Showing papers on "Testosterone published in 1989"
TL;DR: The data suggest interesting relations between environmental and lifestyle factors and serum sex hormones, which are potentially modifiable and, hence, if associations between sex hormones and disease exist, modification of these factors could affect disease risks.
Abstract: Serum sex hormones may be related to the risk of several diseases in postmenopausal women. In the current report, the authors examined the epidemiology of serum sex hormones in 176 healthy, white postmenopausal women (mean age 58 years) recruited from the metropolitan Pittsburgh, Pennsylvania, area. The data were collected during 1982-1983; none of the women were on estrogen replacement therapy. Serum concentrations of estrone, estradiol, testosterone, and androstenedione were measured by a combination of extraction, column chromatography, and radioimmunoassay. Neither age nor time since menopause was a significant predictor of sex hormones. The degree of obesity was a major determinant of estrone and estradiol. The estrone levels of obese women were about 40% higher than the levels of nonobese women. There was a weak relation between obesity and the androgens. Cigarette smokers had significantly higher levels of androstenedione than nonsmokers, with little difference in serum estrogens between smokers and nonsmokers. Both estrone and estradiol levels tended to decline with increasing alcohol consumption. Physical activity was an independent predictor of serum estrone. More active women had lower levels of estrone. There was a positive relation of muscle strength with estrogen levels. The data suggest interesting relations between environmental and lifestyle factors and serum sex hormones. These environmental and lifestyle factors are potentially modifiable and, hence, if associations between sex hormones and disease exist, modification of these factors could affect disease risks.
490 citations
TL;DR: There is a high incidence of anterior pituitary hormone deficiencies in patients treated surgically forpituitary tumours and the incidence increases after external radiotherapy and endocrine testing is recommended on an annual basis.
Abstract: The development of anterior pituitary hormone deficiencies has been studied in a group of 165 patients who underwent external radiotherapy for tumours of the pituitary or closely related anatomical sites, and who have been observed for up to 10 years. One hundred and forty had undergone pituitary surgery before radiotherapy. All patients received external radiotherapy by a three-field technique, giving 3750-4250 cGy in 15 or 16 fractions over 20-22 days. A combined test of anterior pituitary function using insulin hypoglycaemia or glucagon stimulation in conjunction with thyrotrophin and gonadotrophin releasing hormone tests and basal estimations of prolactin, thyroid hormones and testosterone or oestradiol was performed before radiotherapy. This was repeated six and 12 months later and subsequently annually. Before radiotherapy, 18 per cent of patients had normal growth hormone secretion, 21 per cent had normal gonadotrophin secretion, 57 per cent had normal corticotrophin reserve and 80 per cent had normal thyrotrophin secretion. Life table analysis demonstrated increasing incidences of all anterior pituitary hormone deficiencies with time: by five years all patients were growth hormone deficient, 91 per cent were gonadotrophin deficient, 77 per cent were corticotrophin deficient and 42 per cent were thyrotrophin deficient. At eight years, respective incidences of deficiencies were 100, 96, 84 and 49 per cent. Radiation-induced hyperprolactinaemia was seen in 73 patients; mean serum prolactin concentration rose from 227 +/- 11 mU/l to a peak of 369 +/- 60 mU/l at two years and subsequently declined towards the basal value. The primary diagnosis, patient age, sex, irradiated tissue volume and previous surgery were examined as variables that might influence the rate of development of anterior pituitary hormone deficiencies, but none of these factors had a significant effect. The radiation induced hyperprolactinaemia was however more marked in female patients. Although anterior pituitary hormone deficiencies most commonly developed in the order growth hormone, gonadotrophin, corticotrophin, thyrotrophin (61 per cent of patients), other sequences were evident. Most notably corticotrophin deficiency occurred before gonadotrophin deficiency. There is a high incidence of anterior pituitary hormone deficiencies in patients treated surgically for pituitary tumours and the incidence increases after external radiotherapy. Deficiencies may occur in an unpredictable sequence and endocrine testing is recommended on an annual basis.
419 citations
TL;DR: The intrauterine position phenomenon provides the only mammalian model for relating postnatal traits to concentrations of endogenous hormones to which individuals are exposed during fetal life and one specific hypothesis is that circulating estradiol may interact with testosterone in mediating some aspects of sexual differentiation in rodents and, thus, possibly in other mammals.
Abstract: In rodents and swine, individual differences in a broad range of characteristics correlate with intrauterine position during fetal life. By identifying the intrauterine position of mice at cesarean delivery, we can predict reliably postnatal reproductive traits such as genital morphology, timing of puberty, length of estrous cycles, timing of reproductive senescence, sexual attractiveness, sexual behavior, aggressiveness, daily activity level, body weight and tissue enzyme activity in females; in males we can predict genital and brain morphology, sexual behavior, aggressiveness, daily activity level, body weight, and tissue enzyme activity. In mice, as in all mammals, male fetuses have greater concentrations of testosterone than do females. In addition, female mouse fetuses have greater circulating concentrations of estradiol than do male fetuses, a condition not found in all mammals. A mouse fetus positioned between males has greater concentrations of testosterone than does a fetus of the same sex positioned between females, and a fetus positioned between females has greater concentrations of estradiol than does a fetus of the same sex positioned between males. Gonadal steroids regulate differentiation of secondary sexual characteristics. Studies in which the effects of intrauterine position have been eliminated by exposing fetuses to steroid receptor blockers reveal the critical role of steroids in mediating this phenomenon. The intrauterine position phenomenon provides the only mammalian model for relating postnatal traits to concentrations of endogenous hormones to which individuals are exposed during fetal life. Results from studies using this naturally occurring experimental system in litter-bearing species have given insights concerning the consequences of individual differences in steroid concentrations during sexual differentiation that likely apply to all mammals. One specific hypothesis is that circulating estradiol may interact with testosterone in mediating some aspects of sexual differentiation in rodents and, thus, possibly in other mammals.
322 citations
TL;DR: DNA sequence analysis demonstrates that the liver and ventral prostate forms of steroid 5 alpha-reductases are identical hydrophobic proteins of 29 kDa, and suggests that the steroid 5AlphaReductase gene is differentially regulated by testosterone in androgen-responsive versus non-responsive tissues.
249 citations
TL;DR: The plasma levels of DHEAS, DHEA, delta 4-dione are markedly different between men and both animal models used and measurements of prostatic levels of androgens suggest that the high plasma Levels of these steroids are likely responsible for the presence of important amounts of DHT in human prostate after castration.
223 citations
TL;DR: Northern and slot blot analyses demonstrated that castration lowered ang-n mRNA levels in the male kidney by greater than or equal to 60% compared with control, suggesting that androgen may be involved with renal ang- n gene regulation.
Abstract: Renal angiotensinogen (ang-n) mRNA concentration in the male WKY rat increases significantly during puberty. Furthermore, renal angiotensinogen mRNA level in the adult female WKY rat is considerably lower than in the male. The present study investigates the role of androgen in differential renal ang-n mRNA expression. Northern and slot blot analyses with alpha-32P labeled ang-n cDNA (pRang 3) demonstrated that castration lowered ang-n mRNA levels in the male kidney by greater than or equal to 60% compared with control, suggesting that androgen may be involved with renal ang-n gene regulation. Moreover, male WKY rats castrated as weanlings and normal adult female WKY rats each implanted with testosterone displayed significant (P less than 0.05) increases in renal ang-n mRNA levels. Our observations, taken together with previous reports that androgen influences proximal tubule morphology and the tubular expression of transport proteins (e.g., Na+/H+ antiporter), may have important physiological implications for understanding the relationship between androgen and angiotensin in the regulation of tubular function.
192 citations
TL;DR: It is concluded that nilutamide can prevent the adverse consequences of the buserelin-induced transient rise in plasma testosterone levels in men with advanced prostate cancer treated with a GnRH analogue.
Abstract: Gonadotropin-releasing hormone (GnRH) analogues administered for the treatment of advanced prostatic cancer induce a transient increase in plasma testosterone levels during the first week of treatment, often with a secondary rise in plasma levels of prostatic acid phosphatase and a flareup of disease. To determine whether the antiandrogen nilutamide (Anandron) blocks these effects, we carried out a multicenter, placebo-controlled study of nilutamide in men with prostatic cancer treated with the GnRH analogue buserelin. Thirty-six men with disseminated prostatic cancer and elevated plasma levels of prostatic acid phosphatase were randomly assigned to two groups. Group 1 included 17 men who received buserelin (500 micrograms daily subcutaneously) and nilutamide (300 mg daily by mouth); group 2 included 19 men treated with buserelin and placebo. Symptoms were assessed, and plasma was collected before treatment, daily for 14 days, and on days 18, 22, and 29 after the initiation of treatment. Bone pain appeared or worsened in 5 of the 17 men in group 1 and in 12 of the 19 men in group 2 (P less than 0.05). Acute urinary obstruction occurred in one man in group 2. Despite similar changes in the plasma testosterone levels in both groups, the median concentration of plasma prostatic acid phosphatase decreased almost immediately in group 1, but increased transiently, then decreased on day 14 in group 2. Median levels of prostate-specific antigen decreased immediately in group 1 and decreased on day 8 in group 2. We conclude that nilutamide can prevent the adverse consequences of the buserelin-induced transient rise in plasma testosterone levels in men with advanced prostate cancer treated with a GnRH analogue.
190 citations
TL;DR: Findings consistent with criteria for the pathological diagnosis of polycystic ovaries, that is 3 of the 4 findings listed above, were present in 18 of the 26 subjects (69.2%).
Abstract: Polycystic ovarian disease (PCOD) is associated with elevated serum LH and (sub)normal FSH levels, while serum androgen levels are often elevated. To clarify the role of androgens in this abnormal pattern of gonadotropin secretion, LH secretion was studied in 1) 9 eugonadal female to male transsexual subjects before and during long term (6 months) testosterone (T) administration (250 mg/2 weeks, im), and 2) in a woman with an androgen-secreting ovarian tumor both before and after surgical removal of the tumor. Finally, we studied the effects of high serum androgen levels on ovarian histology in 3) 26 transsexual subjects after long term (9–36 months) T administration (250 mg/2 weeks, im) to assess whether T-induced ovarian abnormalities are similar to those that occur in women with PCOD. Long term T treatment in the nine female to male transsexual subjects resulted in increases in the mean serum T level from 1.7 ± 0.8 (±sd) to 40.8 ± 31.9 nmol/L (P < 0.01), the mean serum dihydrotestosterone leve...
183 citations
TL;DR: Findings indicate that perinatal gonadal steroids influence the number of cells within the AVPv that express TH in detectable amounts by determining thenumber of cells that are capable of producing sufficient quantities of TH message, as opposed to sex-specific alterations in the post-translational mechanisms.
166 citations
TL;DR: The results suggest that activin inhibits testosterone formation by the Leydig cells derived from normal mature rats, and inhibin alone has no effect, but reverses the inhibitory action of activation.
Abstract: Inhibin and activin are gonadal glycoproteins that selectively inhibit and stimulate FSH release, respectively. Previously we have reported that transforming growth factor-beta inhibited hCG-stimulated testosterone formation in mature Leydig cells. In the present study we evaluated the effects of other members of the transforming growth factor-beta family, inhibin and activin, on Leydig cell function. We found that activin (0.1-10 ng/ml) had no effect on basal testosterone formation, but inhibited hCG-stimulated testosterone formation in a dose-dependent manner. Activin (10 ng/ml) inhibited hCG-stimulated testosterone formation by 42%. Activin also inhibited hCG-stimulated cAMP formation. In the presence of activin (5 ng/ml), forskolin (10 microM)- and 8-bromo-cAMP (0.1 mM)-induced testosterone formation were reduced about one third. Conversions of pregnenolone and progesterone to testosterone were also blocked by activin. Interestingly, [125I]hCG binding to Leydig cells and forskolin-induced cAMP formation were not affected by the addition of activin. In contrast to activin, inhibin (0.1-10 ng/ml) had no effect on hCG-induced testosterone formation at any concentration used. However, the inhibitory effects of activin on Leydig cell function were reversed by the concomitant addition of inhibin. Our results suggest that activin inhibits testosterone formation by the Leydig cells derived from normal mature rats. Multiple steps of the steroidogenic pathway are affected by testosterone. Inhibin alone has no effect, but reverses the inhibitory action of activin.
152 citations
TL;DR: A direct in vitro effect of 17 beta-estradiol (E2) was demonstrated on bone and cartilage cell energy metabolism and it is possible that direct sex-specific actions of gonadal steroids may contribute to stimulating bone growth and maintaining balanced bone turnover.
Abstract: A direct in vitro effect of 17 beta-estradiol (E2) was demonstrated on bone and cartilage cell energy metabolism. Sex-specific stimulation by E2 and testosterone was shown in diaphyseal bone of weanling rats. E2 (30 nM) caused, within 24 hr, a 70-200% increase in creatine kinase (CK; ATP:creatine N-phosphotransferase, EC 2.7.3.2) specific activity in ROS 17/2.8 rat osteogenic sarcoma cells, MC3T3-E1 mouse calvaria-derived cells, and rat fetal calvaria cells, and a 40% increase in rat epiphyseal cartilage cells. Stimulation of CK activity by E2 was dose and time dependent: in ROS 17/2.8 cells, a highly significant increase was found at 3 nM E2 and a greater than 100% increase in CK activity was found 1 hr after E2 administration. In female 20-day-old Wistar-derived rats, E2 (5 micrograms per rat) increased CK activity in diaphyseal bone by 82% within 1 hr of i.p. injection, with a maximal increase of 200% after 24 hr; neither the weakly estrogenic agonist 17 alpha-estradiol, testosterone, nor progesterone showed this effect. Conversely, in male rat diaphyseal bone, testosterone or dihydrotestosterone increased CK activity after 24 hr by approximately 100%, while E2 was ineffective. In epiphyseal cartilage, both E2 and testosterone increased CK activity. Stimulation of CK activity by sex hormones was paralleled by significant increases in [3H]thymidine incorporation into DNA. Therefore, it is possible that direct sex-specific actions of gonadal steroids may contribute to stimulating bone growth and maintaining balanced bone turnover.
TL;DR: Steroid autoradiography was undertaken to determine the neuroanatomical loci which might be involved in the activation of steroid-sensitive behaviors in the Japanese quail (Coturnix japonica).
Abstract: Steroid autoradiography was undertaken to determine the neuroanatomical loci which might be involved in the activation of steroid-sensitive behaviors in the Japanese quail (Coturnix japonica). Male and female quail were either surgically gonadectomized or photically regressed and implanted with androgen or estrogen to restore normal sexual and courtship behavior. After gonadectomy or implant removal, each quail was injected with 250 microCi of [3H]-testosterone (3H-T), [3H]-estradiol (3H-E2), or [3H]-dihydrotestosterone (3H-DHT), sacrificed, processed for autoradiography, and the telencephalon, diencephalon, mesencephalon, and rhombencephalon were examined for labelled cells. Following 3H-T or 3H-E2 injection and autoradiography, labelled cells were found in nucleus septalis lateralis (SL), nucleus preopticus medialis (POM), nucleus paraventricularis (PVN), regio lateralis hypothalami (LHy), nucleus inferior hypothalami (IH), nucleus infundibuli (IN), nucleus intercollicularis (ICo), substantia grisea centralis (GCt), nucleus taeniae (Tn), and in the reticular formation near nucleus motorius nervi trigemini (MV). In addition, following 3H-E2 autoradiography, labelled cells were found around nucleus accumbens (Ac). Following 3H-DHT autoradiography, labelled cells were found only in SL, PVN, Tn, LHy, ICo, and CGt. No labelled cells were found in Ac, POM, IH, IN, or MV even after long exposure times. These results suggest that the nuclei labelled following 3H-E2 but not 3H-DHT administration bind exclusively the aromatized metabolites of T. Since quail show a sex difference in male-typical copulatory behavior in response to E2, labelled cells were counted in POM, LHy, IH, and Tn of male and female quail following 3H-E2 injection and autoradiography. No sex differences in the number of labelled cells were found in POM, LHy, or IH. Males were found to have more labelled cells than females in Tn. These results show that sex differences in male-typical copulatory behavior are not due to sex differences in the number of cells binding estrogens in POM. The results reported here constitute the most neuroanatomically extensive report of steroid binding cells to date for a galliform brain, the first comparison in a galliform bird of the distributions of cells labelled following injection of 3H-T, 3H-E2, and 3H-DHT and the first analysis of sex differences in numbers of estrogen-binding cells in four nuclei in the avian brain.
TL;DR: The data suggest that in a vegetarian group, less testosterone is available for androgenic action, and both, androstane-3 alpha, 17 beta-diol glucuronide and androstan-3 beta,17 beta-Diol glucuride concentrations are significantly correlated with SHBG levels and with the FAI values.
TL;DR: Serum samples were obtained from 6860 men during their study examination from 1971 to 1975 and their stored sera and that of 98 matched controls from the study population were tested for testosterone, dihydrotestosterone, estrone, estradiol, and sex hormone globulin.
TL;DR: It is demonstrated that serum prostate-specific antigen is related to prostatic size, prostatic epithelial weight, and testosterone stimulation, and there is tremendous variation in the relative amount of epithelium in a prostate.
TL;DR: Evidence of alteration(s) in adrenocortical steroidogenesis has been presented suggesting a selective obesity-related enhancement in adrenal androgen secretion, which may arise secondary to the influence of other circulating and intra-adrenal factors.
TL;DR: Results suggest that even after prolonged use of extremely high doses of anabolic steroids, sperm production may return to normal and percentages of motile and normally formed sperm were significantly reduced in bodybuilders compared with normal volunteers.
TL;DR: The data suggest that relatively high and prolonged levels of E2R occupation are required for estrogen activation of male sexual behavior, and that in intact male rats T, acting via androgen receptors, plays a primary role in mediating the expression of masculine sexual behavior.
Abstract: The purpose of this study was 2-fold: 1) to use gonadal steroid hormone exposures in the physiological range to assess the relative roles of testosterone (T), estradiol (E2), and dihydrotestosterone (DHT) in the expression of male sexual behavior, and 2) to determine whether androgen receptor (AR) or estrogen receptor (E2R) occupation is increased after exposure to these various gonadal steroid hormones. Sexually experienced, castrated male rats implanted sc with Silastic capsules containing T, 10% E2, DHT, 10% E2 plus DHT, or blanks provided hormone levels in the physiological range. Copulatory behavior was measured on days 2-4, 5-7, 10-12, and 14-16 of steroid treatment. Although T, E2, and E2 plus DHT treatments all activated mounting, only T was effective in restoring ejaculation in 100% of the males. DHT alone had no effect on any aspect of male sexual behavior. Brains of males given these various hormone treatments were assayed for both cell nuclear AR and cell nuclear E2R binding in the hypothalamus, preoptic area, amygdala, and septum. Results indicate that when hormone levels in the physiological range were employed, T and DHT bind primarily to AR, whereas E2 binds to E2R. In a second experiment, 0.5% E2 plus DHT was found to yield AR and E2R levels comparable to those in rats receiving T capsules. Male rats bearing these capsules showed virtually no sexual behavior, demonstrating that elevation of AR and E2R levels comparable to those generated by T is not sufficient to induce male sexual behavior. We then measured intact AR and E2R levels and determined that in intact males E2R levels were higher than in T-treated males. These E2R levels could be replicated using 1.0% E2. Males exposed to 1.0% E2 plus DHT failed to display male sexual behavior. These data suggest that 1) relatively high and prolonged levels of E2R occupation are required for estrogen activation of male sexual behavior, 2) high levels of AR occupation induced by DHT are not sufficient to activate male sexual behavior, and 3) in intact male rats T, acting via androgen receptors, plays a primary role in mediating the expression of masculine sexual behavior.
TL;DR: The effects of pure FSH and/or LH preparations on the number of Leydig cells and their function in immature hypophysectomized rats have been investigated and pregnenolone production perLeydig cell in LH-treated rats was only slightly different from the hypophy sectomized controls.
Abstract: The effects of pure FSH and/or LH preparations on the number of Leydig cells and their function in immature hypophysectomized rats have been investigated. As a result of hypophysectomy at the age of 17-18 days, the number of recognizable Leydig cells per testis decreased, as did the steroidogenic capacity in vivo and in vitro. Treatment with 64 micrograms FSH on both 22 and 23 days of age, did not affect the number of recognizable Leydig cells. In contrast, two injections of LH (10 micrograms) caused a sixfold increase in the number of Leydig cells, but had a negative effect on spermatogenesis. These stimulatory and inhibitory effects of LH diminished when FSH was added. Treatment with FSH for 7 days caused a twofold increase in the number of Leydig cells when compared with hypophysectomized controls. 3 beta-Hydroxysteroid dehydrogenase (3 beta-HSD) and esterase activity in Leydig cells also increased under the influence of FSH. The pregnenolone production per Leydig cell in the presence of 5-cholesten-3 beta,22(R)-diol (22R-hydroxycholesterol) as substrate showed a sevenfold increase. Plasma testosterone levels 2 h after injection of human chorionic gonadotrophin in intact rats and hypophysectomized FSH-treated rats were the same. Following LH treatment for 7 days, the number of Leydig cells proved to be 11 times higher, and 3 beta-HSD and esterase activity were not different from intact controls. The testicular pregnenolone production was four- to fivefold higher when compared with untreated hypophysectomized rats. However, pregnenolone production per Leydig cell in LH-treated rats was only slightly different from the hypophysectomized controls.(ABSTRACT TRUNCATED AT 250 WORDS)
TL;DR: Amniotic fluid samples from midgestation were assayed for levels of testosterone and follicle-stimulating hormone, and significant sex differences were observed, with some degree of overlap between the sexes.
Abstract: In humans, the influence of prenatal sex hormones on the fetal brain and subsequent postnatal development has had limited study because of the apparent inaccessibility of hormone levels in normal fetuses. We propose that amniotic fluid obtained via midtrimester amniocentesis can be assayed for fetal hormone levels during the period thought to be important for sexual differentiation of the brain. Amniotic fluid samples from midgestation (N = 70) were assayed for levels of testosterone and follicle-stimulating hormone, and significant sex differences were observed (ps less than .001), with some degree of overlap between the sexes. The possibility of applying hormone levels obtained from amniotic fluid to the study of postnatal development is discussed.
TL;DR: It is suggested that FSH is involved in the maintenance of spermatogenesis in the adult rat and that the effects of FSH are not mediated through changes in intratesticular androgens.
Abstract: In order to clarify further the role of FSH in the maintenance of spermatogenesis, adult rats were treated with purified human FSH (2 X 5 IU/day per rat), testosterone (1.5 cm silicone elastomer implant) or a combination of both hormones for 2 weeks following hypophysectomy. After hypophysectomy alone, no elongate spermatids were observed and the numbers of pachytene spermatocytes and round spermatids observed were reduced when compared with untreated controls. Testosterone supplementation alone qualitatively maintained the formation of elongate spermatids in most seminiferous tubules, whilst in FSH-treated rats increased numbers of round spermatids and pachytene spermatocytes were observed when compared with hypophysectomized animals. Formation of elongate spermatids, however, did not occur under FSH treatment alone. A combination of FSH and testosterone treatment maintained spermatogenesis in an almost quantitative fashion. Numbers of pachytene spermatocytes and round spermatids were maintained at about 80% of levels seen in intact control animals. Treatment with FSH or testosterone alone maintained testis weights at significantly higher levels than those seen in hypophysectomized controls (FSH, 0.79 +/- 0.05 g; testosterone, 0.81 +/- 0.07 g; hypophysectomized, 0.50 +/- 0.04 g). Animals treated with FSH and testosterone showed testis weights 20% below control values (1.22 +/- 0.05 vs 1.51 +/- 0.06 g; P less than 0.05). No increases in intratesticular or intratubular androgen concentrations or in testosterone: dihydrotestosterone ratios were observed in any of the hormone-treated groups when compared with hypophysectomized controls. In all hypophysectomized animals testicular androgen concentrations were reduced to less than 5% of control values. The results obtained in this study suggest that FSH is involved in the maintenance of spermatogenesis in the adult rat and that the effects of FSH are not mediated through changes in intratesticular androgens. Low levels of testosterone in combination with FSH can almost quantitatively maintain spermatogenesis in adult rats.
TL;DR: In this review, Brian Metcalf and colleagues focus on the chemical and kinetic mechanisms of steroid 5 alpha-reductase, and known inhibitors of this enzyme, and discuss the rationale behind the design of a mechanistically distinct class of steroid5 alpha- reductase inhibitors.
TL;DR: Hypertensive men had lower levels of both free and total testosterone and androstenedione than controls and the converse was true for hypertensive women, and testosterone levels were similar in blacks and whites regardless of gender or blood pressure.
Abstract: Little is known about the relationship between blood pressure and endogenous sex steroid hormones in patients with essential hypertension. Studies in hypertensive men have described decreased androgens. Men with cardiovascular disease may have estrogen levels which are increased or similar to healthy controls. We measured selected sex steroid hormones in 24 medication-free patients with uncomplicated essential hypertension (diastolic blood pressure less than or equal to 90 mmHg) and 24 normotensive subjects. The groups were equally divided by race, gender, age and weight. Hypertensive men had lower levels of both free and total testosterone and androstenedione than controls. The converse was true for hypertensive women. Androgen levels were similar in blacks and whites regardless of gender or blood pressure. Estradiol levels were higher in hypertensive men and women than controls and in blacks than whites. Levels of luteinizing hormone and sex hormone binding globulin were similar in all subjects. The clinical and pathophysiological significance of our findings merits further investigation.
TL;DR: Rat Leydig cells possess functional high affinity receptors for corticotropin-releasing factor (CRF), and it is demonstrated that CRF-induced inhibition of the acute steroidogenic action of hCG is exerted at sites related to receptor/cyclase coupling or cAMP formation.
TL;DR: It is concluded that liver tumor promotion by testosterone requires a functional androgen receptor in the intact animal, however, this promotion is not cell autonomous; that is, the response of the preneoplastic hepatocyte is not dependent on the expression of functional receptors in the target cell.
Abstract: Tfm (testicular feminization) mutant mice lack functional androgen receptors. By studying liver tumor development in Tfm mice, we have shown that the greater susceptibility of male mice relative to female mice for liver tumor induction by N,N-diethylnitrosamine is androgen receptor-dependent. C57BL/6J normal and Tfm mutant mice were injected at 12 days of age with N,N-diethylnitrosamine (0.2 mumol/g, i.p.), and liver tumors were enumerated in 50-week-old animals. Normal males averaged 20 liver tumors per animal; Tfm males, 0.7; normal females, 0.6; and Tfm/+ heterozygous females, 1.5. The androgen receptor gene and the Tfm mutation are X chromosome linked. Because of random X chromosome inactivation, hepatocytes from Tfm/+ heterozygous female mice are mosaic with respect to the expression of mutant or wild-type receptors. To determine if testosterone acts directly as a liver tumor promoter, through the androgen receptor in preneoplastic hepatocytes, or by an indirect mechanism, we chronically treated these mosaic female mice with testosterone and measured the androgen receptor content of the resulting tumors. B6C3F1 Tfm/+ mosaic and +/+ wild-type female mice were injected i.p. at 12 days of age with N,N-diethylnitrosamine (0.1 mumol/g) and ovariectomized at 8 weeks of age. Half of the mice of each group subsequently received biweekly s.c. injections of testosterone (0.15 mg per mouse) for 30 weeks. Tumor multiplicity was the same for wild-type and Tfm/+ mosaic females treated with testosterone (31-32 tumors per animal at 38 weeks of age) and was increased relative to females not treated with testosterone (13-17 tumors per animal at 50 weeks of age). Testosterone treatment did not significantly increase the percentage of androgen receptor-positive tumors in Tfm/+ mosaic females: 58% of the tumors from Tfm/+ mosaic females treated with testosterone were receptor positive compared to 48% in Tfm/+ females not treated with testosterone and 92% in wild-type females treated with testosterone. Finally, the number of androgen receptors in the majority of liver tumors examined was greatly decreased relative to the surrounding normal liver tissue. We conclude that liver tumor promotion by testosterone requires a functional androgen receptor in the intact animal. However, this promotion is not cell autonomous; that is, the response of the preneoplastic hepatocyte is not dependent on the expression of functional receptor in the target cell.
TL;DR: The similarity of thePOA sites for activation of mounting by TP and EB is consistent with the hypothesis that cells within the POA aromatize testosterone to estrogens, which directly stimulate the cellular processes leading to behavioral activation.
TL;DR: It is concluded that pharmacological castration resulting from 3-month treatment with a long-acting GnRH agonist decreases the intraprostatic T concentration and those of DHT and 3 alpha-diol to about one tenth of the levels in untreated men.
Abstract: The intraprostatic concentrations of testosterone (T) and dihydrotestosterone (DHT) have been measured in only a few men We measured, in prostatic tissue obtained at surgery from seven men with benign prostatic hyperplasia, the effects of 3-month treatment with a long-acting GnRH agonist on 1) the intraprostatic concentrations of T, DHT, and 5 alpha-androstan-3 alpha, 17 beta-diol (3 alpha-diol); 2) prostatic 5 alpha-reductase activity; and 3) the prostatic content of androgen receptors (AR) Plasma T, DHT, and 3 alpha-diol levels also were measured Prostatic tissue samples obtained at surgery from a group of untreated men with benign prostatic hyperplasia also were studied The mean DHT and 3 alpha-diol concentrations in the prostatic tissue of the treated men were about 10% of those in untreated men (n = 19; P less than 001 for DHT and P less than 005 for 3 alpha-diol), and the mean intraprostatic T concentration in the treated men was about 25% of that in the control group (010 greater than P greater than 005) The mean in vitro formation of DHT by the prostatic tissue of the treated men was about 50% lower (P less than 005) than that by prostatic tissue of the untreated men (n = 9) The mean cytosolic AR content in the prostatic tissue of the treated men was significantly higher (P less than 005), whereas the mean nuclear content of both salt-extractable and salt-resistant AR was significantly lower (P less than 005) than that in the prostatic tissue of the untreated men (n = 8) The mean plasma T levels in treated men decreased from 477 +/- 179 (SD) ng/mL (165 +/- 62 nmol/L) to 027 +/- 042 ng/mL (09 +/- 15 nmol/L) after 1 month of therapy and remained in the castrate range thereafter We conclude that pharmacological castration resulting from 3-month treatment with a long-acting GnRH agonist decreases the intraprostatic T concentration to about one fourth and those of DHT and 3 alpha-diol to about one tenth of the levels in untreated men Thus, GnRH agonist treatment may not completely abolish intraprostatic androgen concentrations in metastatic prostatic cancer patients The decrease in prostatic 5 alpha-reductase activity as well as the decrease in nuclear receptors are probably secondary to the decrease in plasma T concentrations
TL;DR: Results indicated that TP treatment significantly attenuated neuronal loss in prepubertal and young adult female rats in a dose- and time-dependent manner.
Abstract: This study was undertaken to elucidate whether (1) administration of testosterone to female rats attenuates axotomy-induced neuronal loss; (2) the efficacy of testosterone treatment is related to the age of animals, the dosage given, and the time and duration of the treatment; (3) neurons which project or terminate aberrantly can survive; and (4) the trophic actions of testosterone on neuronal survival and axonal outgrowth are operated under the same mechanisms. The hypoglossal and facial nerves were transected unilaterally at 3 and 6 weeks of age. In order to establish the dose-response curve, testosterone propionate (TP) at doses of 0.5, 1.0, 2.0, or 5.0 mg was injected subcutaneously twice weekly during the first 4 postaxotomy weeks, and once weekly thereafter for an additional 6 weeks. Neuronal numbers in the hypoglossal and facial motor nuclei were counted 10–12 weeks after axotomy in serial paraffin sections stained with cresyl violet. To determine the time course of TP effect, neuronal numbers were counted at 1, 4, 12, and 20 weeks after axotomy. In addition, neuronal loss 12 weeks after axotomy in rats treated with TP for the first 3 postaxotomy weeks only was compared with that in rats withheld TP treatment until the 5th postaxotomy week. To determine axonal projections and terminations of the surviving neurons, HRP retrograde tracing technique was used. Results indicated that TP treatment significantly attenuated neuronal loss in prepubertal and young adult female rats in a dose- and time-dependent manner. Only doses which elevated serum testosterone to levels comparable to or surpassing normal male levels were effective.(ABSTRACT TRUNCATED AT 250 WORDS)
TL;DR: Testis weights, serum testosterone, and STF-T concentrations remained significantly reduced in LH- and GnRH-immunized rats that did not receive testosterone supplementation, and the rats remained azoospermic.
Abstract: The ability of testosterone to quantitatively restore spermatogenesis in rats made azoospermic by active immunization against LH or GnRH was examined. Sexually mature adult male rats (n = 15/group) were actively immunized against ovine LH or GnRH-human serum globulin conjugate, while control rats (n = 10) were injected with saline. After 10 weeks of immunization, five rats per group were euthanized. For each rat, trunk blood was collected for determination of LH, FSH, and testosterone by RIA; seminiferous tubule fluid (STF) was collected from one testis per rat, and testosterone concentration was measured by RIA; the number of advanced spermatids per testis was determined from the contralateral testis. The results obtained after 10 weeks of treatment were as follows. 1) Serum LH and FSH were undetectable by RIA in GnRH-immunized rats. 2) Serum testosterone was undetectable in both the LH- and GnRH-immunized groups. 3) The testosterone concentration in STF (STF-T) was reduced from the control valu...
TL;DR: These studies demonstrate that these female-predominant hepatic P-450 enzymes are regulated by different mechanisms, and that both are under hormonal regulatory controls distinct from those that govern expression of the female-specific hepatic enzymes.
Abstract: Hepatic expression of cytochrome P-450j (alcohol- inducible nitrosamine demethylase; P-450 gene IIE1) and P- 450 3 (testosterone 7α-hydroxylase; P-450 gene IIAl) is female predominant in adult rats [female/male = 1.5-2 (P-450j) or 3-4 (P-450 3)]. This sex difference emerges during the postsuckling period, when P-450 3 declines significantly (60-70% decrease) in male, but not female, rats, and P-450j declines in both sexes, but to a lower constitutive level in males than in females. The biochemical factors and regulatory events that control these developmental changes were investigated and found to be distinct from those that regulate expression of the female-specific hepatic enzymes P-450 2d (P-450 gene IIC12) and steroid 5α-reductase. Immunoquantitation of the changes in P-450j and P- 450 3 levels in hormonally altered rats established that both P- 450s are under gonadal control. However, while androgen and estrogen both suppress P-450j expression, estrogen stimulates and androgen suppresses the expressi...