Showing papers on "Testosterone published in 1976"

The effects of androgens and antiandrogens on hormone-responsive human breast cancer in long-term tissue culture.

Abstract: We have examined five human breast cancer cell lines in continuous tissue culture for androgen responsiveness One of these cell lines shows a 2- to 4-fold stimulation of thymidine incorporation into DNA, apparent as early as 10 hr following androgen addition to cells incubated in serum-free medium This stimulation is accompanied by an acceleration in cell replication Antiandrogens [cyproterone acetate (6-chloro-17alpha-acetate-1,2alpha-methylene-4,6-pregnadiene-3,20-dione) and R2956 (17beta-hydroxy-2,2,17alpha-trimethoxyestra-4,9,11-triene-1-one)] inhibit both protein and DNA synthesis below control levels and block androgen-mediated stimulation Prolonged incubation (greater than 72 hr) in antiandrogen is lethal The MCF- cell line contains high-affinity receptors for androgenic steroids demonstrable by sucrose density gradients and competitive protein binding analysis By cross-competition studies, androgen receptors are distinguishable from estrogen receptors also found in this cell line Concentrations of steroid that saturate androgen receptor sites in vitro are about 1000 times lower than concentrations that maximally stimulate the cells Changes in quantity and affinity of androgen binding to intact cells at 37 degrees as compared with usual binding techniques using cytosol preparation at 0 degrees do not explain this difference between dissociation of binding and effect However, this difference can be explained by conversion of [3H]-5alpha-dihydrotestosterone to 5alpha-androstanediol and more polar metabolites at 37 degrees An examination of incubation media, cytoplasmic extracts and crude nuclear pellets reveals probable conversion of [3H]testosterone to [3H]-5alpha-dihydrotestosterone Our data provide compelling evidence that some human breast cancer, at least in vitro, may be androgen dependent

The Hormonal Activity of the Postmenopausal Ovary

Abstract: The origin of plasma sex hormones in postmenopausal women was studied by determining plasma levels under basal conditions, after ACTH stimulation, and after dexamethasone suppression, as well as after hCG stimulation. Values obtained in postmenopausal women were compared with values observed during the follicular phase of the cycle in young women on the one hand, and with values in ovariectomized women of postmenopausal age on the other hand. All sex steroid levels studied with the exception of estrone, were significantly lower in postmenopausal women than in young women during the early follicular phase of the cycle. In ovariectomized women only androgen levels (testosterone, androstenedione, dihydrotestosterone, and to a lesser extent dehydroepiandrosterone,) were lower than in normal postmenopausal women, estrogen, 17 hydroxyprogesterone, and progesterone levels being similar. ACTH increased all plasma steroid levels except estradiol, whereas after dexamethasone, all sex hormone levels were significantly decreased. hCG stimulation finally caused an increase of borderline statistical significance in testosterone, dehydroepiandrosterone, and 17-hydroxyprogesterone levels. We have concluded from this study that the adrenal cortex is almost the exclusive source of plasma estradiol, estrone, progesterone, and 17OH progesterone and the most important source of plasma dehydroepiandrosterone; that the postmenopausal ovary appears to be responsible for about 50% of plasma testosterone and 30% of androstenedione levels; and that hCG stimulation with 5000 IU daily for 3 days, hardly influences steroid secretion by postmenopausal ovaries.

Pituitary-Gonadal Relations in Infancy: 2. Patterns of Serum Gonadal Steroid Concentrations in Man from Birth to Two Years of Age

Abstract: Testosterone, estradiol, 17OH-progesterone, and androstenedione (except in cord samples) concentrations were determined in cord sera (30 male and 14 female) and in peripheral sera from infants (121 male and 110 female), age 1 day to 2 years. Male and female cord serum levels of these steroids were not significantly different. In both sexes levels during the first week were lower than those in cord sera. In male infants serum testosterone and 17OH-progesterone levels rose sharply in die second week of life, reached a peak at 1–2 months, and then declined to the range seen in later childhood by 6 months of age; male serum androstenedione and estradiol concentrations were higher during the first 2 months of life, but no distinct pattern of rise and fall was seen. In girls serum testosterone levels fell in the first week to the range seen throughout childhood; serum concentrations of estradiol, androstenedione, and 17OH-progesterone in girls were markedly variable, with many values above the childhoo...

Evidence for inhibin-like activity in bovine follicular fluid.

Abstract: THE negative feedback action of testicular steroids on circulating levels of luteinising hormone (LH) is well known. It is less clear how the testis influences follicle-stimulating hormone (FSH). The existence of ‘inhibin’, a water-soluble testicular product that inhibits the secretion of FSH, was first postulated in 1932 (ref. 1); recently, inhibin activity has been detected in rete testis fluid2, testicular tissue3, spermatozoa4 and seminal plasma5. Immunisation of rabbits with the inhibin fraction of bull seminal plasma has produced an antiserum which raised plasma FSH levels when injected into male and female rats6. It has been suggested7 that, in the male, inhibin may be produced by the Sertoli cells of the testis. If this is the case, one wonders if inhibin could also be produced by granulosa cells of the ovary. We have, therefore, looked for the presence of a specific FSH-suppressing agent in ovarian follicular fluid by comparing the effects of fluid and peripheral plasma on the levels of FSH and LH in newly castrated male rats.

Dihydrotestosterone binding by cultured human fibroblasts. Comparison of cells from control subjects and from patients with hereditary male pseudohermaphroditism due to androgen resistance.

Abstract: Dihydrotestosterone binding was measured in culture fibroblasts from 14 control subjects and from 12 patients with five different types of hereditary male pseudohermaphroditism. Two assays of binding were used--an intact monolayer assay and density gradient centrifugation of cell extracts. In the intact monolayer assay of normal cells the uptake of [3H]dihydrotestosterone consisted of two components. The first was a high affinity component that exhibited saturation at approximately 1 nM dihydrotestosterone. The second was a low affinity component that was not saturable with concentrations of steroid up to 5 nM. Twice the number of high affinity binding sites were present in fibroblasts grown from genital skin (foreskin, labia majora, and scrotum) as from nongenital sites (37 vs. 14 fmol/mg protein). In the density gradient assay in 5-10% sucrose, the major peak of dihydrotestosterone binding was in the 8S region in low molarity buffer and in the 4S region in 0.5 M KCl. High affinity binding was normal in cells from two patients with familial incomplete male pseudohermaphroditism, type 2, an autosomal recessive defect in which dihydrotestosterone formation is deficient, and in cells from a patient with male pseudohermaphroditism due to 17 beta-hydroxysteroid dehydrogenase deficiency, an autosomal recessive defect of testosterone synthesis. High affinity binding was low by both methods in fibroblasts from five patients with complete testicular feminization. Furthermore, binding by both methods was also low in cells from three subjects with familial incomplete male pseudohermaphroditism, type 1, a presumed X-linked recessive disorder of androgen resistance, and in fibroblasts grown from a subject with the incomplete form of testicular feminization. The finding that dihydrotestosterone binding is abnormal in two forms of hereditary androgen resistance in addition to complete testicular feminization suggests either that these disorders are the result of allelic mutations affecting the function of the androgen-binding protein or that normal dihydrotestosterone binding requires the participation of more than one gene product.

Plasma adrenal and gonadal sex steroids in human pubertal development.

Abstract: Plasma free dehydroepiandrosterone (DHA), androstenedione (delta), testosterone (T), dihydrotestosterone (DHT), estrone (E1), and estradiol (E2) were measured by radioimmunoassay in 55 boys and 54 girls 3.5 to 16.3 years of age. Plasma DHA increased significantly between 6 and 8 years of age in girls and between 8 and 10 years of age in boys. A further significant increase was noted between 10 and 12 years of age in both sexes. Delta rose significantly between 8 and 10 years of age in girls and between 10 and 12 years in boys. In contrast, no significant increase in T, DHT, or E1, was noted prior to 12 years of age in both sexes. However, E2 showed a significant increase between 10 and 12 years of age in girls. This early rise in the course of pubertal development of the two sex steroids predominantly of adrenal origin, DHA and delta, and its occurence 1 to 2 years earlier in girls than in boys, as does puberty itself, suggest a possible role for these steroids in the mechanisms involved in triggering the hypothalamic-pituitary-gonadal axis at puberty.

A study of the endocrine manifestations of hepatic cirrhosis.

Abstract: The clinical features and hormonal abnormalities were surveyed in 117 men with cirrhosis of the liver. Compared with healthy men of similar ages, the patients had significantly lower metabolic clearance rates, plasma production rates and total and free levels of testosterone, reduced testosterone responses to human chorionic gonadotrophin stimulation, higher oestradiol, luteinizing hormone and follicle stimulating hormone levels and higher binding capacities of sex steroid binding globulin. The peripheral conversion of testosterone to oestradiol was also found to be significantly increased. However, the metabolic clearance and plasma production rates of oestradiol were not significantly different from those of healthy men. Patients who were severely ill with liver failure and one with haemochromatosis had low levels of luteinizing hormone and follicle stimulating hormone and sub-normal responses to clomiphene and luteinizing hormone-releasing hormone. Higher plasma oestradiol levels were found in patients with gynaecomastia and spider naevi than in those without these signs. However, the clinical features of androgen deficiency--that is, testicular atrophy, impotence and loss of secondary sex hair--were only poorly related to the low testosterone levels, and production rates and longtitudinal studies indicated that the hormonal levels, endocrine features and severity of the liver disease could change independently. It is concluded that the clearance of oestradiol from plasma is not limited by liver disease in all patients, and that reduced degradation of oestrogens is not the initial event in the sequence leading to the hormonal abnormalities of cirrhosis. While gonadotrophin deficiency occurs with liver failure and in some patients with haemochromatosis, the more usual findings are of elevated gonadotrophin levels and a poor Leydig cell response to chorionic gonadotrophin. These suggest that the hypogonadism is primary in most patients with cirrhosis. The causes of the high oestradiol levels were not discovered. Increased peripheral conversion of precursors to oestradiol or increased testicular secretion of oestradiol are possibilities. The high binding capacities of sex steroid binding globulin were not significantly correlated with either the low testosterone or high oestradiol level and the cause of this abnormality remains uncertain. The low metabolic clearance rates of testosterone appeared to result from the increased plasma protein binding of testosterone. The discrepancies in the expected relationships between the hormone and clinical changes suggest that factors other than those studied are also involved in the genesis of the endocrine features of hepatic cirrhosis.

Androgens augment FSH-induced progesterone secretion by cultured rat granulosa cells.

Abstract: Granulosa cells have been isolated from ovaries of estrogen-treated immature intact and hypophysectomized rats, and have been maintained in culture in a chemically-defined medium. Progesterone secretion by these cells was stimulated by the addition of FSH to the medium. In the presence of 0.5 uM testosterone or 17β-OH-5α-androstan-3-one (DKT), progesterone secretion was low or undetectable. However, the addition of testosterone or DHT together with FSH caused a dramatic 8- to 19-fold increase over that caused by FSH alone. On the other hand, luteinizing hormone (LH) alone had no effect on progesterone secretion, but produced a small stimulation when added together with testosterone. These results demonstrate synergism between androgens and FSH in the control of progesterone secretion by granulosa cells in culture.

Hormonal dynamics associated with the menopause.

Abstract: The current understanding of androgen estrogenand gonadotropin metabolism in menopausal women is reviewed. In young women the principal ovarian androgen is androstenedione (mean concentration 1500 pg/ml; range 500-3000 pg/ml; and production rate 3 mg in 24 hours). During the menstrual cycle its concentration is 15% higher at midcycle. Increased ovarian secretion is thought to cause this increase. In blood androstenedione is bound loosely to albumin and minimally to sex-hormone-binding globulin (SHBG). The circulating level of testosterone ranges from 200 to 600 pg/ml. Its mean concentration is 20% higher at midcycle. Testosterone is bound extensively to globulin. The average production rate of testosterone is 250 mcg in 24 hours. Of circulating androstenedione 14% is converted to testosterone accounting for 50% of circulating testosterone. After ovariectomy androstenedione of adrenal origin accounts for most of the testosterone. The remainder is the result of direct adrenal secretion of testosterone. In normal postmenopausal women the mean androstenedione concentration is half the concentration found in intact premenopausal women and is similar to that in younger patients after ovariectomy. The clearance rate is the same in older and in younger women. In postmenopausal women ovariectomy results in a small but significant decrease in circulating androstenedione. The adrenal glands secrete comparable amounts of androstenedione before and after the menopause. For testosterone the mean concentration is lower in postmenopausal women but higher than after ovariectomy in young women. The clearance rate does not change. In young women the principal circulating estrogen is 17beta-estradiol. Its level fluctuates widely during each cycle with the highest level prior to ovulation. Estradiol is also bound to SHGB. The production rate varies greatly during each cycle. Most estradiol is secreted by the ovary. Postmenopausal estradiol levels are low and the clearance level is reduced. Estrone levels vary during the menstrual cycle. It is not bound to the SHGB. The metabolic clearance rate is rapid and the production rate changes during the cycle. In postmenopausal women the clearance rate of estrone is lower. The source is then from the peripheral conversion of androstenedione. In postmenopausal women with endometrial cancer or endometrial hyperplasia excessive conversion has been shown with increased estrone production. In cancer patients excessive body weight seemed to be a factor in increasing circulating levels of these hormones. As women approach the menopause follicle stimulating hormone levels rise while luteinizing hormone (LH) levels tend to remain the same. In postmenopausal women both levels are significantly elevated. Marked pulsatile variations in gonadotropin release have been observed. Low estrogen levels are thought to cause increased responsiveness of the pituitary to LH-releasing factor. Endometrial cancer patients may have different gonadotropin activity.

Control of renal vitamin D hydroxylases in birds by sex hormones.

Abstract: Kidney homogenates from adult male Japanese quail or chickens demonstrate hydroxylase activity predominantly for the 24 rather than the 1 position of 25-hydroxyvitamin D3 (25-hydroxycholecalciferol). A single injection of 5 mg of estradiol-17beta into a male bird completely suppresses the 24-hydroxylase and greatly increases the 1-hydroxylase activity. Immature males do not respond well to estrogen alone, but they do respond well to estradiol plus testosterone. Testosterone alone has little or no effect on the hydroxylases of either species. Castrated male chickens show an estradiol response only when testosterone is also given. Optimal 24 hr responses to 5 mg of estradiol per kg in the castrate male were obtained with about 12 mg of testosterone per kg. These optimal amounts of estradiol and testosterone increased the activity of 25-hydroxyvitamin D3-1-hydroxylase approximately 225-fold (this enzyme is also known as 25-hydroxycholecalciferol 1-monooxygenase; 25-hydroxycholecalciferol, NADPH: oxygen oxidoreductase (hydroxylating), EC 1.14.13.13). These results demonstrate a strong regulation by the sex hormones of the renal vitamin D hydroxylases in birds.

Testicular Function after Orchiopexy for Unilaterally Undescended Testis

Abstract: Testicular function was determined in 29 men, 21 to 35 years old, who had undergone orchiopexy for unilaterally undescended testis at four to 12 years of age. Serum testosterone and dialyzable testosterone concentrations of these men were not significantly different from those of a control group of 30 normal men, and their basal serum luteinizing hormone concentrations and serum luteinizing hormone responses to synthetic gonadotropin-releasing hormone were only slightly higher than those of the normal men. The mean sperm density of the patients, however, was only one third of that of the normal men (P<0.001). The mean serum follicle stimulating hormone response to gonadotropin-releasing hormone of the patients was double that of the normal men (P<0.001). The data indicate that spermatogenesis may be abnormal after orchiopexy, and suggest that men with unilaterally undescended testis may have bilateral testicular abnormality. (N Engl J Med 295:15–18, 1976)

Regulation by steroid hormones of phosphorylation of specific protein common to several target organs

Abstract: The effect of in vivo administration of steroid hormones on the endogenous phosphorylation of individual proteins in cell sap from several target tissues has been studied using the technique of discontinuous sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The hormones studied (and their respective target organs) were: 17 beta-estradiol [1,3,5(10)-estratriene-3, 17beta-diol] (uterus); testosterone (17 beta-hydroxy-4-androsten-3-one) (ventral prostate and seminal vesicle)' cortisol (11beta, 17alpha, 21-trihydroxy-4-pregnene-3,20-dione) (liver); aldosterone (the 18.11-hemiacetal of 11beta,21-dihydroxy-3,20-dioxo-4-pregnen-18-al) (toad bladder). In each of the five target organs studied, pretreatment with the appropriate hormone reduced the amount of 32P incorporated from [gamma-32P]ATP into an apparently common protein band present in the cytosol fraction. The endogenous phosphorylation and dephosphorylation of this protein was also regulated by cAMP. This protein, designated SCARP (steroid and cyclic adenosine 3':5' monophosphate regulated phosphoprotein), was estimated to have an apparent molecular phoprotein), was estimated to have an apparent molecular weight of 54,000 in the gel electrophoresis system used. The effect of the steroid hormones in decreasing the phosphorylation of SCARP was specific for their respective target tissues. The effect of 17beta-estradiol and of testosterone on SCARP could be observed as early as two hours after a single dose of the steroid. A protein synthesis inhibitor, cycloheximide, abolished the effect of the steroid hormones, but not that of cAMP, on the endogenous phosphorylation of SCARP. The results suggest that steroid hormones regulate either the amount of SCARP or its ability to become phosphorylated. This regulation of a single species of protein by several types of steroid hormones in different target organs raises the possibility that this common biochemical action may be a component of the mechanism by which these steroids achieve some of their biological effects.

Androgen Receptors in the Anterior Pituitary and Central Nervous System of the Androgen “Insensitive” (Tfm) Rat: Correlation Between Receptor Binding and Effects of Androgens on Gonadotropin Secretion

Abstract: The cytosol fractions of the anterior pituitary, hypothalamus, preoptic area and brain cortex of androgen “insensitive” (Tfm) rats possess androgen receptors. However, in the Tfm rats the androgen binding per mg protein was only 10–15% of that in the corresponding normal littermates (Nl). The physicochemical properties of the androgen receptors in the anterior pituitary of the Tfm rat were indistinguishable from those of the normal rat. Thus, no distinctive differences were observed with regard to electrophoretic mobility in 3.25% polyacrylamide gels, isoelectric point (pI = 5.8), binding affinity (KD = 1.5 × 10−9M), temperature stability, sulfhydryl dependence and steroid specificity. It is, therefore, likely that the very low androgen binding capacity by the anterior pituitary and the central nervous system is due to an extreme reduction in the receptor number rather than to the presence of abnormal receptors. Since in the Tfm animals the androgen receptor number is reduced by 85–90%, il: is to be expec...

Idiopathic Hirsutism — An Ovarian Abnormality

Abstract: We investigated increased production of testosterone and androstenedione in 44 women with unexplained adult-onset hirsutism, 41 of whom had Normal-Sized ovaries. Twenty women in this group had at least 50 per cent suppression of plasma testosterone and androstenedione after four to five days of dexamethasone. Testosterone and androstenedione values in ovarian-vein effluents were higher than those of their adrenal veins. We calculated adrenal secretion rates of both androgens in each patient by relating the adrenal gradients to those of cortisol. In 42 of the hirsute women, including those whose androgens were suppressed after dexamethasone, the ovaries were the predominant source of androgen production. The women with dexamethasone suppression had milder degrees of virilism and lower production rates of testosterone and androstenedione. We conclude that the ovaries are the source of excessive androgens in most women with unexplained hirsutism, and that corticoid-suppressible patients have milder ...

Effects of Sex Steroids on Prolactin Secreting Rat Pituitary Cells in Culture

Abstract: A clonal strain of rat pituitary tumor cells (GH3) was used to study the effects of different sex steroids on the production of prolactin (PRL). Hormone production was measured by radioimmunoassay and expressed as the amount of hormone which accumulated in the medium of monolayer cultures during 24 h. The stimulatory effect of 17β-estradiol (10−11M-10−6M) on PRL production was significant after 4 days and the maximum effect (300% of control cultures) was observed at 10−8M after 10 days of treatment. After removal of added 17β-estradiol, the production of PRL returned to control levels in 5 days. Progesterone (10−11M-10−6HM) caused a doserelated decrease in PRL production reaching 60% of control values at 10−6M. Testosterone (10−6M) stimulated the production of PRL (130% of controls), whereas 5α-dihydrotestosterone (10−6M) had a small effect (107% of controls) which was not always reproducible. None of the sex steroids affected cell growth. Progesterone (10−6M) inhibited the stimulatory effect of 17β-estra...

Intratesticular Site of Aromatization in the Human

Abstract: To determine the intratesticular site of aromatization, homogenates of separated seminiferous tubules and intact tissue from human testes were incubated with [3H] androstenedione or [3H] testosterone. [3H] Estrogens were isolated and identified, and the amounts synthesized were expressed as pmol/mg protein incubated. In testicular tissue from the three adult subjects investigated, the total estrogen per mg protein was 1.5-2.7 times greater in intact tissue than in isolated seminiferous tubules. This suggests that the major site of aromatization in human testes is the interstitial tissue. Estradiol was by far the major estrogenic product. No differences were observed in the amount of estrogens synthesized whether the substrate was androstenedione or testosterone.

Regulation of serum gonadotropins by photoperiod and testicular hormone in the Syrian hamster.

Abstract: Male hamsters were maintained on long (14L:10D) or short (10L:14D) photoperiods. The serum concentrations of LH and FSH were reduced in the animals kept on the short photoperiod, and these animals had atrophied testes and sex accessories. Serum gonadotropin concentrations increased following castration in both long and short photoperiods, but gonadotropin secretion was inhibited by much smaller doses of testosterone in the males maintained on the short photoperiod as comapred to males kept on a long photoperiod. The levels of testosterone required to suppress serum gonadotropin levels in castrated animals corresponded reasonably well with the serum androgen levels observed in intact males, suggesting that serum androgen is a major regulator of gonadotropin secretion in the male hamster.

The control of spermatogenesis in the green frog, Rana esculenta

Abstract: The process of spermatogenesis in Rana esculenta (living in the surroundings of Naples) resurges gradually in the spring months, proceeds actively through the summer and declines gradually in the winter months reaching an almost total “quiescence” for a short length of time. The repeating from year to year with a distinct regularity of spermatogenetic cycle suggests that environmental cues play a role in timing its various phases. Both temperature and photoperiod appear to be potential modifiers of spermatogenetic activity in this species. It is, however, probable that photoperiod acts only in a permissive way to facilitate the temperature response which seems to be the more direct modifier of the testicular activity. The proliferation of primary spermatogonia seems to be favoured by only low temperatures. The formation of secondary spermatogonia, and primary and secondary spermatocytes occurs when there occurs a gradual increase in the ambient temperature, day length and gonadotropin secretion. This period is characterized by very low plasma level of testosterone, that, through the reduced negative feedback to the hypothalamus, favours an increased secretion of FSH-like gonadotropin. Spermatid formation is entirely androgen-dependent as confirmed by the use of a specific antiandrogen, cyproterone acetate. In fact spermatid formation naturally occurs in a period when plasma level of testosterone is increasing and pituitary gonadotrops are declining in their secretory activity. In this period the ambient temperature and the photoperiod gradually decline. The importance of lateral eyes and the pineal gland in the mediation of influence of photic cues has been shown. It seems that without either the eyes or the pineal gland both light and temperature are completely ineffective in stimulating the early spermatogenesis, which shows the permissive role of light on temperature influence upon spermatogenesis. Hypophysectomy impairs spermatogenesis, which can be restored by a replacement therapy with homoplastic pituitary extract. Testosterone alone does not restore spermatogenesis except enhancing spermatid formation. Pituitary extract stimulates mitotic activity of spermatogonia and formation of primary and secondary spermatocytes. Testosterone is not involved because the stimulatory effects of pituitary extract are only marginally blocked by the antiandrogen. In fact spermatogonial multiplication is partially inhibited, while spermatid formation is totally blocked, indicating that ICSH-like gonadotropin acts upon the formation of spermatids through the stimulation of testosterone production. Thus it has been found that there exists a complex interaction between the environmental factors and the “endogenous hormonal trigger” that subsequently steps into the regulation of spermatogenesis.

Plasma follicle-stimulating hormone during photoperiodically induced sexual maturation in male Japanese quail.

Abstract: Follicle-stimulating hormone (FSH) was measured in Japanese quail using a heterologous radioimmunoassay, the specificty of which was confirmed by its cross-reactions with purified chicken FSH and luteinizing hormone (LH). Plasma concentrations of FSH, LH and testosterone were determined in quail during the testicular growth and sexual maturation which follows their transfer from short to long daylengths. All three hormones could be detected in short-day birds but their concentrations were greatly increased following photostimulation. Plasma FSH increased 12-fold during the first 9 long days, remained at this level for a week, and then declined steadily so that by the time the birds were sexually mature the level of FSH had decreased to one-third of the maximum level. LH reached a high level (five times the short day level) after 4 long days. Thereafter two patterns of LH secretion could be distinguished. In one experiment the high level of LH was maintained unchanged throughout sexual maturation while in another experiment LH secretion decreased significantly between days 11 and 28 of photostimulation. A strong correlation existed between testicular growth and the plasma FSH concentration. It was maximal during the phase of rapid testicular growth and decreased as spermiogenesis began. The pituitary FSH content increased during photostimulation. Castration caused a 20-fold rise in plasma FSH compared with that in intact quail. The change in LH concentration after castration was about eightfold. The changes in hormone secretion were strikingly similar to those found during sexual development and puberty in the rat.

Androgen levels in the plasma and prostatic tissues of patients with benign hypertrophy and carcinoma of the prostate

Abstract: Specific radioimmunoassays for testosterone, dihydrotestosterone (DHT) and androstenedione were carried out to measure the concentrations of the three hormones in the plasma and prostatic tissue of ten patients with benign prostatic hypertrophy (BPH) and ten patients with carcinoma of the prostate. The results indicate that there are no significant differences between the peripheral plasma concentrations of testosterone, DHT and androstenedione in BPH [19.7 +/- 2.6, 2.6 +/- 0.9 AND 5.5 +/- 1.7 (S.E.M.) nmol/l respectively] and in carcinoma [16.9 +/- 2.8, 2.4 +/- 0.5, 4.4 +/- 1.1 nmol/l respectively], (in all cases P greater than 0.1). In contrast, the prostate tissue rations DHT: testosterone (3.59 +/- 0.55 for BPH and 0.66 +/- 0.09 for carcinoma) and androstenedione: testosterone (2.83 +/- 0.38 for BPH and 1.07 +/- 0.16 for carcinoma) are significantly less in carcinoma than in benign hypertrophy ( in all cases P less than 0.01). The accumulation of testosterone in the carcinoma, relative to values found in BPH tissue is, therefore, not associated with changes in the concentrations of androgens in the plasma pool but may be related to local factors and metabolic changes within the prostate.

Inherited congenital normofunctional testicular hyperplasia and mental deficiency.

Abstract: Four 46,XY siblings with congenital bilateral megalorchidia, macrogenitosomia, and severe mental deficiency were investigated. The testicular size was significantly larger than age-matched normal males. A normal hypothalamic-pituitary gonadotropin function was demonstrated by the finding of normal levels of luteinizing and follicle-stimulating hormones in blood samples drawn at frequent intervals and by normal responses to gonadotropin-releasing hormone and testosterone adminstration. A normal testicular function was shown by the finding of normal (a) plasma testosterone and estradiol levels, (b) gonadal response to human chorionic gonadotropin, (c) sperm analysis, and (d) morphology and cell architecture of the testes. Adrenal function was found to be within normal limits. These results demonstrated the existence of normofunctional testicular hyperplasia. The family studies suggested that this distinct congenital disorder is inherited as an X-linked recessive trait.

Edward T. Tyler Prize Oration: LH-releasing hormone and its analogues: recent basic and clinical investigations.

Abstract: Literature on luteinizing hormone-releasing hormone (LH-RH) and its analogues is reviewed LH-RH which stimulates the release of both luteinizing hormone (LH) and follicle stimulating hormone (FSH) is active in numerous species It has been postulated that the release and synthesis of FSH and LH is mediated by an interaction between sex steroids and hypothalamic LH-RH Administration of antiserum to LH-RH has been shown to block the preovulatory LH surge and ovulation in laboratory animals which suggests an immunological approach to fertility control It appears that LH-RH is rapidly broken down by dispersed liver anterior pituitary and kidney cells Cyclic AMP has been shown to act as a mediator of LH-RH and FSH release Although LH-RH has potential diagnostic value its effectiveness in differentiating various types of hypogonadism is not clearly established Generally sex steroids diminsh the responses to LH-RH though estrogens have both a stimulatory and inhibitory effect Glucocorticoids have been shown to suppress the LH response to LH-RH LH-RH has been effective in inducing ovulation in anovulatory women and in treating men with hypogonadotropic hypogonadism Stimulatory and inhibitory analogues of LH-RH and their clinical application are reviewed

Sex Hormone Binding Globulin : The Carrier Protein For d-Norgestrel

Abstract: The binding of different synthetic steroids, used in hormonal contraception, to Sex Hormone Binding Globulin (SHBG)was studied by measuring their ability to displace tritiated testosterone from SHBG in a competitive protein binding system. Only 19-nortestosterone derivates had any significant ability to displace testosterone from SHBG, dnorgestrel (d-Ng) being the strongest displacer. Increasing the SHBG levels in women with previous constant plasma d-Ng levels increased these levels two-to sixfold. It is concluded that SHBG is the main carrier protein for d-Ng. The strong testosterone displacing activity of d-Ng might also explain androgenic side effects observed with d-Ng containing oral contraceptives.

Failure of Estrogens and Androgens to Inhibit Bone Resorption in Tissue Culture

Abstract: The effects of estrogens, androgens, and glucocorticoids on bone resorption were compared in organ culture. At a concentration of 10−5M, corticosterone, testosterone, dihydrotestosterone, dehydroepiandosterone, estradiol, ethinyl estradiol, and estrone did not inhibit the release of 45Ca from 19-day fetal rat long bone shafts in control or parathyroid hormone (PTH)-treated cultures after 2 or 5 days. Cortisol inhibited both control and PTH-stimulated resorption at 10−5 and 10−6M. 17β-Estradiol was inhibitory at 3 × 10−4M. However, it was less effective than the estrogenically inactive epimer 17α-estradiol, in 8 day control cultures or in cultures containing low concentrations of PTH. At 10−5M, neither 17β-estradiol nor 17α-estradiol inhibited resorption stimulated by prostaglandin E2 or by osteoclast activating factor. (Endocrinology 98: 1065, 1976)

Effects of morphine and methadone on serum testosterone and luteinizing hormone levels and on the secondary sex organs of the male rat.

Abstract: The effects of morphine and methadone on the endocrine control of the male rat's sexual function were examined. The results indicate that these narcotics markedly reduce the structural and functional integrity of the secondary sex organs by producing a pronounced reduction in serum testosterone levels. Serum levels of luteinizing hormone (LH) were not detectable in narcotic-treated animals, whereas serum levels of the follicle stimulating hormone (FSH) were unaltered. On the basis of these observations, it seems reasonable to conclude that the narcotics inhibit the secretion of LH, by an action either in the hypothalamus (e.g., suppression of LH-releasing hormone) or directly in the pituitary gland, which leads to a reduction in serum testosterone levels and a subsequent reduction in the wet-tissue weight and secretory activity of the secondary sex organs.