Showing papers on "Testosterone published in 1987"
TL;DR: It is suggested that androgen may be critical for the maintenance of optimal levels of sexual functioning in postmenopausal women.
Abstract: Five aspects of sexual behavior were monitored daily in three groups of women who had undergone total abdominal hysterectomy and bilateral salpingo-oophorectomy approximately 4 years ago for benign disease. One group had been receiving an estrogen-androgen preparation intramuscularly once a month since their surgery (E-A). The second group had been receiving estrogen alone (E) and the third group of women had remained untreated. Plasma estradiol and testosterone were measured at an established baseline and again on days 2, 4, 8, 15, 21, and 28 postinjection. Women who received both sex steroids reported higher rates of sexual desire (p less than 0.01), sexual arousal (p less than 0.01), and numbers of fantasies (p less than 0.01) than those who were either given E or who were untreated. Moreover, changes in these behaviors covaried with plasma testosterone but not with plasma estradiol levels during the treatment month as the drug was being metabolized. Rates of coitus and orgasm were also higher in the E-A group during the first two postinjection weeks (p less than 0.01) coincident with their higher testosterone levels. These findings imply that androgen may be critical for the maintenance of optimal levels of sexual functioning in postmenopausal women.
400 citations
TL;DR: The findings suggest that androgens have an important supportive role in established benign prostatic hyperplasia and that testicular suppression will benefit some patients, however, this form of treatment could be applicable only in carefully selected patients who were not surgical candidates, and it would need to be maintained indefinitely.
Abstract: We examined the influence of androgens on benign prostatic hyperplasia, using nafarelin acetate, a potent luteinizing-hormone-releasing hormone agonist, to achieve reversible androgen deprivation in men with benign prostatic hyperplasia. Nine patients with bladder-outlet obstruction due to benign prostatic hyperplasia were treated with subcutaneous nafarelin acetate (400 micrograms per day) in an open trial for six months. In all patients, serum testosterone decreased to castrate levels. Objective observations included uroflowmetry, measurement of residual urine volume, determination of prostatic size by ultrasonography, and prostatic biopsy. In all patients, the prostate regressed to a mean (+/- SEM) of 75.8 +/- 3 percent of the initial size (range, 52 to 86; P less than 0.005); the regression reached a plateau after four months. Morphologic analysis of biopsy specimens showed regression of glandular epithelium. Three of nine patients had clinical improvement with treatment. Six months after the cessation of treatment, plasma testosterone levels had returned to normal and the size of the prostate had increased to 99 +/- 5.5 percent of the initial size. These findings suggest that androgens have an important supportive role in established benign prostatic hyperplasia and that testicular suppression will benefit some patients. However, this form of treatment could be applicable only in carefully selected patients who were not surgical candidates, and it would need to be maintained indefinitely.
321 citations
TL;DR: Results show that Leydig cells from animals deprived of LH had diminished capacity to convert pregnenolone to testosterone and reduced P450 C17-hydroxylase/C17,20-lyase content.
Abstract: Depriving rats of luteinizing hormone (LH) causes Leydig cells to lose smooth endoplasmic reticulum and diminishes their P450 C17-hydroxylase/C17,20-lyase activity (Wing et al., 1984). LH administration to hypophysectomized rats prevents these changes in Leydig cell structure and function (Ewing and Zirkin, 1983). We adopted a multistep procedure of rat Leydig cell isolation to study the trophic effects of LH on steroidogenesis in the Leydig cell. Our method employs vascular perfusion, enzymatic dissociation, centrifugal elutriation, and Percoll gradient centrifugation. The purified Leydig cell fraction obtained after Percoll density-gradient centrifugation contains 95% well-preserved 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD)-staining cells with ultrastructural characteristics of Leydig cells. These Leydig cells produced 248 and 29 ng of testosterone/10(6) Leydig cells when incubated for 3 h with and without a maximally stimulating concentration of ovine LH. Purified Leydig cells obtained from control rats and rats treated with testosterone-estradiol (T-E) implants for 4 days to inhibit LH production were incubated with a saturating concentration (2 microns) of pregnenolone. Leydig cells from control and T-E-implanted rats produced 537 and 200 ng of testosterone/10(6) Leydig cells X 3 h, respectively, suggesting a defect in the steroidogenic reactions converting pregnenolone to testosterone in Leydig cells from T-E-implanted rats. By using rabbit antibodies to the P450 C17-hydroxylase/C17,20-lyase pig microsomal enzyme, immunoblots of one-dimensional sodium dodecyl sulfate polyacrylamide gels of Leydig cell microsomal protein from control and 4- and 12-day T-E implanted rats revealed a continued loss of enzyme as the period of LH withdrawal continues. These results show that Leydig cells from animals deprived of LH had diminished capacity to convert pregnenolone to testosterone and reduced P450 C17-hydroxylase/C17,20-lyase content.
294 citations
TL;DR: The fact that specific abnormalities of androgen metabolism in the female are associated with SLE, and may contribute in some way to morbidity and mortality, is supported and may have implications for future therapeutic regimens based on male hormone replacement.
Abstract: The high ratio of women with systemic lupus erythematosus (SLE) has remained unexplained, despite the recent description of metabolic abnormalities of estrogen and androgen metabolism. Alterations of steroid metabolism in patients with SLE could be important in the pathogenesis of this disease, since it has been reported that gonadal steroids modulate the immune system. Moreover, research with inbred lupus mice has shown that estrogens have adverse effects on the disease in both sexes, whereas androgen therapy or oophorectomy is protective in females. Recently, the finding of elevated testosterone oxidation at C-17 in females with SLE suggested that plasma androgen levels in males and females with SLE should be examined more closely. We studied the varying degrees of clinical activity, with regard to plasma levels of 4 significant androgens: testosterone, androstenedione, dehydroepiandrosterone, and dehydroepiandrosterone sulfate in a series of 5 male and 42 female SLE patients. Decreased levels of all androgens were observed in women with SLE. The lowest levels of plasma androgens were found in female patients who had active disease, as determined by laboratory and clinical assessment. These data support the fact that specific abnormalities of androgen metabolism in the female are associated with SLE, and may contribute in some way to morbidity and mortality. More importantly, these data may have implications for future therapeutic regimens based on male hormone replacement.
275 citations
TL;DR: Chronic confinement for 1 month caused a significant elevation of plasma cortisol but suppressed the levels of plasma testosterone and 11-ketotestosterone in sexually mature male brown trout, and an acute handling stress for 1 hr elevated blood cortisol and ACTH levels and also suppressed circulating androgens.
250 citations
TL;DR: The results indicate that growth hormone acts as a repressive factor for the constitutive and inducible levels of P-450b and P- 450e in a manner different from the regulation ofP-450-male and P -450-female.
168 citations
TL;DR: The ratio of protein to carbohydrate in the human diet is an important regulatory factor for steroid hormone plasma levels and for liver-derived hormone binding proteins, and consistent and reciprocal changes suggest that a change in protein/carbohydrate ratio influences plasma steroid hormone concentrations.
165 citations
TL;DR: Treatment with insulin and testosterone had a synergistic effect on spermatogenesis, and a GnRH stimulation test demonstrated that pituitaries of diabetic animals had a blunted response, with diminished LH and FSH secretion.
161 citations
TL;DR: The data show that the POM volume is controlled by testosterone levels in adulthood and could thus be an interesting model for the study of the effects of steroids on the brain.
153 citations
TL;DR: The data suggest that thermal injury leads to acute inhibition of adrenal and testicular C19-steroid secretion, but stimulation of Adrenal glucocorticosteroid production, and that endocrine function in many instances is not normalized after complete healing of the burned surfaces.
Abstract: The effects of burn trauma in men on the production of adrenal and testicular steroids was investigated. Whereas there were significant increases in serum cortisol levels and urinary 17-hydroxycorticosteroid excretion soon after thermal injury, there were significant decreases in serum dehydroepiandrosterone sulfate, dehydroepiandrosterone, androstenedione, and testosterone concentrations during the first 4 weeks following burn trauma. Serum androstenediol and androstenediol sulfate levels also were reduced, though insignificantly, 10-23 days postburn. Serum LH levels were unchanged during the postburn interval. Since urinary 17-ketosteroid excretion was normal or below normal rather than increased, the decline in serum C19-steroid levels probably resulted from decreased glandular secretion rather than increased rates of metabolism and excretion. Low dehydroepiandrosterone sulfate and/or testosterone levels were found in some men several months after recovery from their burns. These data suggest that thermal injury leads to acute inhibition of adrenal and testicular C19-steroid secretion, but stimulation of adrenal glucocorticosteroid production, and that endocrine function in many instances is not normalized after complete healing of the burned surfaces. The mechanisms and physiological consequences of such changes in the steroid milieu of men after burn trauma are unknown.
148 citations
TL;DR: In this paper, the authors measured the response of serum insulin and androgen concentrations to an 8 A.M. oral glucose tolerance test (OGTT) in ten hyperandrogenic (HA) women and seven midfollicular phase control subjects.
TL;DR: Higher levels of androstenedione, a steroid particularly responsive to stress, were associated with adjustment problems in both boys and girls, reflecting the stress of later maturation.
TL;DR: The relation between sex hormone levels and subsequent risk of a major coronary event was studied in a nested case-control study among 163 men in the Multiple Risk Factor Intervention Trial who later had aMajor coronary event and in 163 controls.
Abstract: The relation between sex hormone levels and subsequent risk of a major coronary event was studied in a nested case-control study among 163 men in the Multiple Risk Factor Intervention Trial who later had a major coronary event and in 163 controls. Cases and controls were matched for age, serum cholesterol level, randomization group, randomization date and clinic. Blood samples were collected at baseline before randomization and frozen at -70 degrees C. Follow-up extended over 6 to 8 years. Sixty-one patients had a nonfatal acute myocardial infarction and 102 fatal infarction. Total and free testosterone, total and free estradiol, androstenedione and estrone concentrations were measured. There were no significant differences between cases and controls for any sex hormone level. There was also no difference in the ratio of testosterone to estradiol. Controlling for other cardiovascular risk factors did not change these results. These results do not support previous case-control studies of a relation between sex hormone levels and risk of heart attack among men.
TL;DR: A new non-steroidal antiandrogen ICI 176,334 (4'-cyano-3-(4-fluorophenylsulphonyl)-2-hydroxy-2-methyl-3'- trifluoromethyl)propion-anilide) has now been discovered which causes regression of the accessory sex organs but does not increase serum concentrations of LH and androgens.
Abstract: Pure antiandrogens, like flutamide, antagonize androgen action both peripherally and centrally at the hypothalamic-pituitary axis, which leads to an increase in LH and testosterone secretion. A new non-steroidal antiandrogen ICI 176,334 [2RS)-4'-cyano-3-(4-fluorophenylsulphonyl)-2-hydroxy-2-methyl-3'- trifluoromethyl)propion-anilide) has now been discovered which causes regression of the accessory sex organs but does not increase serum concentrations of LH and androgens. ICI 176,334 binds to rat prostate androgen receptors with an affinity around fourfold that of hydroxyflutamide. When administered s.c. concurrently with testosterone propionate (200 micrograms/kg) for 7 days to immature castrated rats, ICI 176,334 (10 mg/kg) significantly (P less than 0.001) inhibited growth of the seminal vesicles and ventral prostate gland. Oral administration of ICI 176,334 at doses of 1, 5 and 25 mg/kg for 14 days to adult rats caused a dose-related reduction in accessory sex organ weights but had no effect on the testes. None of these doses caused a significant increase in serum LH and testosterone. Flutamide was around fourfold less potent and significantly increased serum LH and testosterone at the higher doses. ICI 176,334 was well tolerated. ICI 176,334 should, therefore, prove useful for the treatment of androgen-responsive benign and malignant diseases.
TL;DR: The increase in the mean plasma GH level during chronic sex steroid exposure is due mainly to augmentation of GH pulse amplitude, and that sex steroids probably increase spontaneous GH secretion.
Abstract: Sex steroid administration can increase the GH response to provocative stimuli, but the relationship of sex steroids to spontaneous GH secretion is still controversial. We sought to characterize the effect of sex steroids on the plasma GH concentration by examining the 24-h pattern of episodic GH secretion in nine previously untreated adult men with isolated hypogonadotropic hypogonadism before and during long term testosterone, gonadotropin, or pulsatile GnRH treatment. After chronic sex steroid exposure, the mean 24-h plasma GH level, mean GH pulse amplitude, and mean area under the curve of pulses were significantly increased compared to pretreatment values [3.2 +/- 1.8 ( +/- SD) vs. 1.8 +/- 1.2 ng/mL (P less than 0.01); 11.4 +/- 7.2 vs. 5.5 +/- 4.4 ng/mL (P less than 0.05); and 720 +/- 547 vs. 316 +/- 371 ng/mL X 20 min (P less than 0.05), respectively], while mean 24-h pre- and posttreatment GH pulse frequencies were indistinguishable (5.7 +/- 2.1 posttreatment vs. 5.0 +/- 3.2 pretreatment; P = NS). The mean posttreatment plasma somatomedin-C level also rose significantly during treatment (1.89 +/- 0.65 vs. 1.28 +/- 0.48 U/mL; P less than 0.01). We conclude that the increase in the mean plasma GH level during chronic sex steroid exposure is due mainly to augmentation of GH pulse amplitude, and that sex steroids probably increase spontaneous GH secretion.
TL;DR: A higher GH increase in premenopausal women compared with age matched-men and an age-dependent decrease in G HRH-stimulated GH secretion in both sexes is found and in women a significant influence of estradiol on GH secretion after GHRH administration could be demonstrated.
Abstract: The influence of age and sex on human GH secretion is controversial. In previous studies, serum GH responses to arginine and insulin-induced hypoglycemia were significantly higher in pre- and postovulatory women than in men. In contrast, recent studies suggest that GH responsiveness to GHRH is higher in normal young men than in age-matched women. To clarify the question of sex and age influence on GHRH-(1-44)-stimulated GH secretion, we studied 116 normal women and men (with body mass indexes of 18-25 and 19-26, respectively) between the ages of 18 and 95 yr. The peak serum GH increments after GHRH administration were significantly higher in premenopausal women than in age-matched men (P less than 0.003 for the age group 18-30 yr and P less than 0.03 for the age group 30-50 yr, as assessed by analysis of variance). The responses were not different in postmenopausal women and age-matched men. Multiple regression analysis revealed a significant negative correlation between GHRH-induced GH responses (integrated area under the curve) and age in both women (P less than 0.002) and men (P less than 0.001). In addition, we determined basal serum testosterone, estradiol, cortisol, and PRL levels in all subjects. Multivariate regression analysis of the GH responses to GHRH administration revealed a significant positive correlation (P less than 0.01) between serum estradiol and both GH increase and the area under the GH response curve. No correlation was found between GHRH-stimulated GH secretion and basal serum cortisol, testosterone, or PRL concentrations. Our data clearly demonstrate a marked influence of both sex and age on GHRH-stimulated GH secretion. We found a higher GH increase in premenopausal women compared with age matched-men and an age-dependent decrease in GHRH-stimulated GH secretion in both sexes. Furthermore, in women a significant influence of estradiol on GH secretion after GHRH administration could be demonstrated.
TL;DR: A direct effect of sex steroid hormones on in vitro cartilage cell metabolism was demonstrated and an age-dependent stimulatory effect on [35S]sulfate incorporation into newly synthesized proteoglycans was shown.
Abstract: A direct effect of sex steroid hormones on in vitro cartilage cell metabolism was demonstrated. Cells were derived from rabbit fetuses on day 20 of gestation, and from male and female rabbits aged from 2 to 80 days. Testosterone (T), dihydrotestosterone (DHT), or 17 beta-estradiol (E2) (10(-9) -10(-9) M) were added to primary culture of epiphyseal articular chondrocytes. They showed an age-dependent stimulatory effect on [35S]sulfate incorporation into newly synthesized proteoglycans. In cultured rabbit fetal cartilage cells, the maximum active concentration of T and DHT was 10(-9) M with a 40% stimulating effect over control values. E2 was even more active with 80% stimulating effect when added at 10(-8) M. Chondrocytes from animals aged up to 5 days responded poorly and those from animals aged 5-30 days not at all. The response of cells from older animals varied with animal age and sex. T and DHT stimulated chondrocytes from males aged 32-55 days and females aged 40-52 days to about the same extent. E2 stimulated cells from animals of the same ages, but the response of female-derived cells was twice that of male-derived cells. The stimulating effect was dose dependent from 10(-11) to 10(-8) M and maximal at 10(-9) M for T and DHT and at 10(-8) M for E2. Puromycin completely abolished the effect.
TL;DR: Pulsatile LH stimulation of the testes does not appear necessary to maintain T secretion, and Gonadotropin secretory responses are destabilized at higher frequencies of GnRH administration.
Abstract: The effects of increasing the frequency of pulsatile GnRH administration on LH and FSH responsiveness were studied in five GnRH-deficient men who had achieved normal sex steroid levels during prior long term GnRH replacement. Intravenous doses of GnRH were employed that had previously been demonstrated to produce LH and FSH levels in each subject similar to those in normal men. Both acute and chronic changes in pituitary responses were studied after progressive increases in GnRH frequency (from every 120 to 60 min, from 60 to 30 min, and from 30 to 15 min) during three 12-h admissions, each separated by 7 days. During the two intervals between the studies GnRH frequency was 60 and 30 min, respectively. Pituitary responses were characterized by determining the mean serum LH and FSH levels, LH pulse amplitudes, and mean LH and FSH levels which were normalized for the frequency of GnRH administration (nLH and nFSH). As the frequency of GnRH stimulation was increased acutely, mean serum LH levels rose progressively, in contrast to both LH pulse amplitude and nLH levels which decreased, while serum testosterone (T) concentrations remained constant. No further evidence of gonadotroph desensitization occurred after chronic GnRH administration at either 60- or 30-min intervals. At higher frequencies of GnRH stimulation, discrete pulses of LH were not always apparent after injections of GnRH, and in two men, marked destabilization of the gonadotroph responses occurred. Even without detectable LH pulses, serum T levels did not decline during administration of GnRH at intervals as rapid as 15 min. In contrast, there was no change in mean FSH concentrations, although nFSH values decreased progressively as the GnRH frequency was increased. nFSH levels fell to a greater degree than nLH after each increase in GnRH frequency. Thus, pituitary gonadotroph responsiveness to a fixed dose of GnRH decreased as the frequency of GnRH stimulation increased. FSH responsiveness decreased to a greater degree than did LH. Gonadotropin secretory responses are destabilized at higher frequencies of GnRH administration. Pulsatile LH stimulation of the testes does not appear necessary to maintain T secretion.
TL;DR: The profile of activity indicates that the induction of HPOA AA is androgen-specific and, together with the demonstrated time-course of induction, lends further support to the hypothesis that androgens regulate AA through a receptor mechanism and the synthesis of new protein.
Abstract: We studied the time-course and steroid specificity for aromatase induction in the hypothalamus-preoptic area (HPOA) of the adult male rat. Aromatase activity (AA) was measured in tissue homogenates by using a radiometric assay that quantifies the stereospecific production of 3H2O from [1 beta-3H] androstenedione. We found that by 48 h after administration of testosterone, HPOA AA was significantly (p less than 0.01) greater than control values in castrated rats. In contrast, AA was significantly (p less than 0.01) reduced 12 h after castration, and reached its lowest levels by 4 days after castration. Several other steroids, administered in 3-cm Silastic capsules for 7 days, were tested for their capacity to induce hypothalamic AA. In addition to testosterone, only 5 alpha-dihydrotestosterone and 5 alpha-androstane-3 alpha, 17 beta-diol were effective. Neither the stereoisomers of these compounds nor several other steroids, including estradiol, progesterone, and corticosterone, were active. This profile of activity indicates that the induction of HPOA AA is androgen-specific and, together with the demonstrated time-course of induction, lends further support to the hypothesis that androgens regulate AA through a receptor mechanism and the synthesis of new protein.
TL;DR: Small and large human luteal cells have steroidogenic properties similar to those exhibited by follicular thecal and granulosa cells, respectively.
Abstract: Enriched small and large cell fractions were prepared from mature corpora lutea from 15 women in the midluteal phase by enzymatic dissociation, followed by Percoll gradient centrifugation. The steroidogenic function of each cell type was assessed by measuring the gonadal steroids released into the incubation medium. The large cell fraction was estimated to be 97% pure, with minimal contamination by small cells, whereas the small cell fraction was approximately 68% pure, being contaminated with 10% large cells and 22% nonsteroidogenic cells. In the unstimulated state, large cells were approximately 2-fold more potent in progesterone formation and aromatase activity, but only half as potent in androstenedione and testosterone formation as an equal number of small cells. When stimulated with hCG, the small cells responded with significant increases in progesterone, androstenedione, and testosterone release, but the large cells did not. Both cell types secreted estrone and 17 beta-estradiol in the presence of androgen substrate, but the addition of FSH significantly stimulated aromatization only in large cells. Thus, small and large human luteal cells have steroidogenic properties similar to those exhibited by follicular thecal and granulosa cells, respectively.
TL;DR: It is confirmed that mating in the spring induces a surge in E2; E2 also was elevated in a single sample obtained from animals collected in the fall, at a time when the majority of females have recently deposited sperm in their oviducts.
TL;DR: It is considered that a state of stress in males triggered by aggressive interactions following an elevation in plasma testosterone concentration during mating and antagonized by an androgen-dependent decrease in CBG concentration results in suppression of both immune and inflammatory reactions.
TL;DR: In female zebrafish ovulation could be induced by male holding water, testis homogenates, and testis fractions containing steroid glucuronides, indicating steroids glucuronide as ovulation inducers.
TL;DR: The present results indicate that high amplitude GH pulses can be induced by either neonatal or adult androgen exposure, but only the continuous presence of androgens during adult life can induce a GH secretory pattern, consisting of large surges at regular 3-h intervals separated by a low baseline that is characteristic of normal male rats.
Abstract: The interactive effects of androgen exposure during neonatal and adult life on the pattern of GH secretion in adult male rats was investigated. Neonatal rats were orchidectomized or sham-operated on days 1–2 of life and injected immediately postoperatively with testosterone propionate (250 μg, sc) or vehicle. At 90–130 days of age the rats were bled every 20 min between 9 and 17 h from an indwelling intraatrial catheter. Some neonatally gonadectomized, testosterone- or vehicle- treated rats were also given depot testosterone (15 mg/kg, im) 5–10 days before blood sampling. Plasma GH concentrations were measured by RIA, and the pulsatile secretory patterns were analyzed by the PULSAR computer program. Neonatal orchidectomy resulted in a marked suppression (50–75%) of both the height and duration of GH secretory episodes, while baseline GH levels were higher in neonatally gonadectomized males than in sham-operated controls. Neonatal testosterone replacement therapy restored high amplitude GH pulses. However,...
TL;DR: Genetic evidence for both androgen-dependent and independent regulation of AA in the rat brain is provided, as well as specific sites where AA is affected in Tfm rats.
Abstract: To investigate the role of androgen receptors in the regulation of brain aromatase activity (AA) in adult rats, the levels of AA in discrete brain areas of androgen-insensitive testicular feminized (Tfm) rats were compared with those in their normal male littermates (NL). AA was measured in homogenates of brain tissue by using a radiometric assay that quantifies the production of 3H2O from [lβ-3H]androstenedione as an index of estrogen formation. Initially, we assessed the capability of block-dissected tissues to aromatize androgens. We found that the AA in the amygdala and hypothalamus-preoptic area of Tfm rats was significantly lower (p < 0.001) than the AA in NL despite the fact that circulating androgen concentrations in the Tfm were significantly higher. Kinetics studies demonstrated that the apparent Michaelis constant was equivalent for both groups (0.02-0.03 μM)- Administration of testosterone propionate to castrated males produced 3 to 4-fold elevations of AA in NL, but did not affect brain AA in...
TL;DR: It is concluded that highly trained male athletes, like their female counterparts, may have a deficiency of hypothalamic gonadotropin-releasing hormone, which may be caused by the prolonged, repetitive elevations of gonadal steroids and other hormones known to suppress gonadotropic hormone secretion that are elicited by their daily exercise.
TL;DR: It is concluded that progesterone acts centrally through a steroid receptor-mediated mechanism to facilitate respiration in anesthetized and paralyzed male and female cats.
Abstract: We have examined the effect on respiration of the steroid hormone progesterone, administered either intravenously or directly into the medulla oblongata in anesthetized and paralyzed male and female cats The carotid sinus and vagus nerves were cut, and end-tidal PCO2 and temperature were kept constant with servo-controllers Phrenic nerve activity was used to quantitate central respiratory activity Repeated doses of progesterone (from 01 to 20 micrograms/kg, cumulative) caused a sustained (greater than 45 min) facilitation of phrenic nerve activity in female and male cats; however, the response was much more variable in females Progesterone injected into the region of nucleus tractus solitarii, a respiratory-related area in the medulla oblongata, also caused a prolonged stimulation of respiration Progesterone administration at high concentration by both routes also caused a substantial hypotension Identical iv doses of other classes of steroid hormones (17 beta-estradiol, testosterone, and cortisol) did not elicit the same respiratory effect Pretreatment with RU 486, a progesterone-receptor antagonist, blocked the facilitatory effect of progesterone We conclude that progesterone acts centrally through a steroid receptor-mediated mechanism to facilitate respiration
TL;DR: The results suggest that in the testis, as in other steroidogenic tissues, TGF-beta may play a role in the development and maintenance of differentiated function.
TL;DR: The data show that a tissue kallikrein indistinguishable thus far from a urinary kallkrein is widely distributed in brain and pituitary and that levels of enzyme and mRNA are comparable in certain central sites.
Abstract: We have detected tissue kallikrein and kallikrein mRNA in various brain regions with a kallikrein direct RIA and with nucleic acid hybridization using a kallikrein cDNA probe. In the direct RIA, rat urinary kallikrein-like activity was found in the pituitary and pineal glands, hypothalamus, cerebral cortex, cerebellum, and brain stem. Pituitary and pineal gland kallikrein concentrations were significantly higher than those in other regions. Only in pituitary was there a significant difference in tissue kallikrein concentration according to sex, with glands from female rats showing levels 4-fold higher than those from male rats. Kallikrein mRNAs were detected in all of the regions and were about 4-fold higher in female than in male pituitary gland. Northern blot analyses show sex dimorphism of pituitary kallikrein mRNA, similar in size to submandibular gland and kidney mRNA. In castrated male rats, whole pituitary kallikrein content was reduced to 50% of the control value and increased 1.7-fold with testosterone replacement and 18-fold with 17 beta-estradiol treatment. Neither T4 nor cortisol affected whole pituitary kallikrein levels in the castrated male rat, but testosterone decreased pituitary kallikrein in normal female rats by 35%. When anterior pituitary or neurointermediate lobe extracts were separately examined, immunoreactive kallikrein was 10.2- and 1.3-fold higher respectively, in female than in male rat lobes. Estradiol benzoate (30 micrograms/kg) administration increased kallikrein levels 90- and 22-fold, respectively, in the anterior pituitary of gonadectomized male and female rats, while it increased by only 40-50% kallikrein levels in the male and female neurointermediate lobe. In dot blot analysis, kallikrein mRNA levels were increased 5-fold by 17 beta-estradiol in the whole pituitary of castrated male rats. In the cytoplasmic dot hybridization analysis, estradiol benzoate treatment increased kallikrein mRNA levels 54-fold in the anterior pituitary of ovariectomized rats. The data show that a tissue kallikrein indistinguishable thus far from a urinary kallikrein is widely distributed in brain and pituitary and that levels of enzyme and mRNA are comparable in certain central sites. Kallikrein levels in the anterior and neurointermediate pituitaries are differentially regulated by estrogen.
TL;DR: It is indicated that TGF-beta can modulate Leydig cell steroidogenesis and cause a dose dependent inhibition of hCG-stimulated testosterone formation but without effects on basal levels.