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Testosterone secretion is severely impaired after hepatectomy in rat, dog and man.

In 90%-hepatectomized rats, the plasma testosterone level (0.34 +/- 0.07 ng.ml, mean +/- SEM) is significantly lower (P less than 0.001) than in sham operated male rats (1.7 +/- 0.26 ng.ml, mean +/- SEM). In dogs, after 90% hepatectomy, the mean plasma testosterone concentration fell to 1/10 of the plasma testosterone level measured in sham operated animals either 24 or 72 h after surgery. In hepatectomized men, plasma testosterone is markedly decreased in contrast to what is observed after duodeno-pancreatectomy performed under the same conditions of anesthesia. These results suggest that 90% hepatectomy severely alters the Leydig cell function.

Animals↗

Mutually independent effects of adrenocorticotropin on luteinizing hormone and testosterone secretion.

In this study, we examined the effect of ACTH on the sensitivity of the testes to gonadotropin and determined the role of the testosterone (T) negative feedback system in mediating the inhibitory effect of ACTH on LH secretion in adult male rats. ACTH infusion for 3 days reduced basal levels of serum T and the T response to GnRH, but did not alter basal levels of serum LH (immunoreactive) or the LH response to GnRH. These effects required the presence of the adrenal glands. Infusion of corticosterone (B) at a dose that increased serum B concentrations 9-fold had an effect similar to that of ACTH on basal serum T levels and the serum T response to GnRH. Basal levels of serum LH and the serum LH response to GnRH were not affected by B administration. These data suggest that ACTH administration reduces the sensitivity of the testes to LH, resulting in a lower basal level of T and a reduced T response to GnRH. This effect was independent of basal serum LH levels or the LH response to GnRH. It appears that B mediates the effect of ACTH on testicular sensitivity to gonadotropin. In another experiment, ACTH administration for 4 days did not alter serum LH values, but reduced serum T levels in sham-castrated male rats. In contrast, ACTH treatment blunted the increase in serum LH after castration by day 2 of treatment, despite the absence of detectable levels of serum T within 6 h after castration. These data suggest that T is not essential for the inhibitory effect of ACTH on LH secretion to occur. They do not support the hypothesis that ACTH enhances the sensitivity of the hypothalamus and/or pituitary to the negative feedback effects of T.

Adrenalectomy↗

Effects of increased testosterone secretion on the behavior of adult male rhesus living in a social group.

Selected members of an all-male social group of rhesus monkeys were treated with twice-weekly injections of human chorionic gonadotropin (HCG) to determine the effects of the consequently increased androgen secretion on social behavior. Radioimmunoassay of blood samples confirmed significant increases in serum testosterone levels in each of 4 subject, but only 3 of these showed significant behavioral changes. The basic social structure of the group, including the dominance hierarchy, was not disrupted by the treatment with HCG. Rather, the behavioral changes which did not occur appeared to be intensifications of previously existing social relationship.

Aggression↗

Modulation of growth hormone, luteinizing hormone, and testosterone secretion by excitatory amino acids in boars.

Ketamine hydrochloride, an n-methyl-d-aspartate (NMDA) receptor antagonist was used in an experiment that tested the hypothesis that fasting-induced increases in growth hormone (GH) secretion is mediated by excitatory amino acid (EAA) neurotransmission in boars. The effects of the drug on circulating concentrations of luteinizing hormone (LH) and testosterone were also evaluated. Blood was sampled at 15-min intervals for 8 h from 12 boars fitted with jugular vein catheters. At Hours 4 and 6, fasted boars (feed was withdrawn 48 h before the start of blood sampling) received i.m. injections of ketamine (19.9 mg/kg body weight; n=4) or .9% saline (n=4). Boars allowed feed on an ad libitum basis (n=4) received i.v. injections of n-methyl-d,l-aspartate (NMA; 2.5 mg/kg body weight), an NMDA receptor agonist, at Hours 4 and 6. Secretion of GH increased after NMA injections but was unaffected by treatment with ketamine or saline. Circulating concentrations of LH and testosterone were increased by injections of ketamine but were unaffected by injections of NMA or saline. Our results suggest that NMA is a potent GH secretagogue, but do not support the hypothesis that EAA neurotransmission drives the increased GH secretion displayed in fasted boars. Our finding that ketamine increased LH and testosterone release supports the notion that EAA have inhibitory effects on gonadotropin secretion in acutely fasted swine.

Animals↗

Norethindrone inhibition of testosterone secretion by an ovarian Sertoli-Leydig cell tumor.

A woman with severe hyperandrogenemia and virilization was found to have a fall in serum testosterone (T) concentration while taking an oral contraceptive containing norethindrone (500 vs. 164 ng/dL). Subsequent surgical exploration revealed an ovarian Sertoli-Leydig cell tumor. In vitro, the tumor secreted T (mean, 1.88 ng/mg X 4 h). hCG did not stimulate T secretion. In addition, norethindrone inhibited T secretion (0.33 ng/mg X 4 h). We conclude that norethindrone directly suppressed T production by the Sertoli-Leydig cell tumor.

Adult↗

The effect of FSH on LH induced testosterone secretion in the immature hypophysectomized male rat.

The effect of gonadotropin pretreatment of hypophysectomized male rats on LH stimulated serum testosterone concentrations was studied. A 5 day pretreatment period began 2 days after hypophysectomy at 21 or 24 days of age. On the day following the pretreatment period the animals received an intraperitoneal injection of saline or LH 60 min before blood collection. Animals pretreated with NIH-FSH-B1, or with doses of LH approximating the amount present in the NIH-FSH, had increased testosterone concentrations after LH stimulation compared to similarly stimulated saline pretreated animals. Pretreatment with more highly purified FSH Ex 199C at a lower dose than the minimum effective dose of NIH-FSH was also effective. There was no synergistic or additive effect when FSH Ex 199C and LH pretreatments were combined. FSH Ex 199C is more potent and contains appreciably less LH contamination than NIH-FSH-B1. The results obtained using FSH Ex 199C indicate that FSH, independent of LH contamination, can increase testes response to LH stimulation.

Animals↗

Regulation of testosterone secretion by prolactin in male rats.

The goal of this study was to characterize the mechanism by which hyperprolactinemia alters testosterone production in rat testicular interstitial cells (TICs). Hyperprolactinemia was induced by grafting 2 anterior pituitary (AP) glands under the subcapsular space of the kidney in experimental rats. Control rats were grafted with brain cortex (CX). Six weeks post-grafting, rats were challenged with human chorionic gonadotropin (hCG) then, the changes in either plasma testosterone or luteinizing hormone was measured. Additionally, TICs were isolated and challenged in vitro with hCG or prolactin, and the testosterone release measured by radioimmunoassay. Further investigation in signal transduction as intracellular 3':5' cyclic adenosine monophosphate (cAMP) production was observed under a regulation of forskolin or SQ22536. After the challenge of hCG or GnRH, the AP-grafted rats showed a suppressed response in testosterone release as compared to those in the CX-grafted group. The in vitro data from the AP-grafted rats compared to the CX-grafted animals showed a diminished response in testosterone release upon hCG stimulation. Administration of forskolin or SQ22536 disclosed dysfunction of adenylate cyclase in TICs from the AP-grafted rats. When 8-Br-cAMP was incubated with TICs, the testosterone production was lower in the AP-grafted compared to the CX-grafted group. These results suggest that in addition to adenylate cyclase dysfunction, inefficiency of post-cAMP pathways are also involved in the hypogonadism elicited by hyperprolactinemia in rats.

Animals↗

Effects of surgery on testosterone secretion in male patients with pituitary adenomas.

The purpose of this study was to assess the effect of surgery on gonadal function in 42 male patients with pituitary adenomas Gonadal functions were evaluated by measuring total serum testosterone concentrations pre- and postoperatively. The subjects of the study were 20 patients with GH secreting adenoma, 7 patients with prolactinoma and 15 patients with nonfunctioning (NF) adenoma. Their ages ranged from 18 to 60 years (mean +/- SEM, 41 +/- 1.9). The serum testosterone concentration was low at less than 300 ng/dl preoperatively in 14 of 20 patients (70%) with GH producing adenoma, 6 of 7 patients (86%) with prolactinoma, and 7 of 15 patients (47%) with NF adenoma. Postoperatively, the total serum testosterone concentration was normalized in 9 of 14 patients (64%) with GH producing adenoma, one of 6 patients (17%) with prolactinoma, and 5 of 7 patients (71%) with NF adenoma. The normalization of serum GH and prolactin concentrations is indispensable for the restoration of gonadal function. It is very important to preserve the normal preoperative gonadotropin secretion by means of gentle surgery.

Adenoma↗

Collagen stability, testosterone secretion and meat tenderness in growing bulls and steers.

Interrelationships among concentrations and maturation of intramuscular collagen, serum concentration of hydroxyproline and testosterone and meat tenderness were determined in growing bulls and steers. Sixty-four Charolais X Angus bulls were assigned to sex treatment groups (intact or castrate) and slaughter groups (9, 12, 15 or 18 mo of age). Animals were bled at 30-min intervals via intrajugular catheters between 0600 and 1400 beginning 48 h before slaughter. Serum concentrations of testosterone were determined in each sample from bulls and from four samples from steers; serum hydroxyproline was determined in the last sample from both sexes. Testosterone mean values for the collection period were calculated. Samples of the longissimus, semitendinosus and infraspinatus muscles secured within 45 min postmortem were analyzed for intramuscular collagen concentration, percent soluble collagen and collagen thermal shrinkage temperature. Tenderness of loin steaks was determined by Warner-Bratzler shear test. Serum concentrations of hydroxyproline and testosterone were higher (P less than .01) in bulls than steers. Age effects were noted for both hydroxyproline (P less than .01) and testosterone (P less than .06). Total intramuscular collagen was greater (P less than .01) in bulls than steers and was different (P less than .01) among muscles, but the muscle differences were not uniform over all ages (P less than .05). Percent soluble collagen declined (P less than .01) with age and was different (P less than .01) among muscles. Interaction of age and muscle (P less than .01) and age and sex (P less than .05) also were noted for percent soluble collagen.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Alcohol decreases the alpha subunit, LH and testosterone secretion in response to LH-RH].

UNLABELLED: In our previous study we showed that alcohol disturbed the circadian rhythms of LH, testosterone and its conversion to DHT. To determine the effect of LH-RH on pituitary-gonadal function before and after alcohol, 11 male volunteers aged 24-29 years (mean 25.5) were investigated. Blood for hormonal estimations was withdrawn before and 20, 30, 60, and 120 min after LH-RH. In every case, the LH-RH test was performed twice: 6 hours after placebo and, a week later, 6 hours after alcohol administered orally, in dose of 1.0 g/kg bw. The LH, FSH, alpha-subunit and testosterone concentrations were measured with radioimmunological methods. RESULTS: It was shown that alcohol significantly inhibited LH (p < 0.05), alpha-subunit (p < 0.02) and testosterone (p < 0.001) response to LH-RH stimulation, but not that of FSH.

Adult↗

Estradiol and testosterone secretion by human, simian, and canine testes, in males with hypogonadism and in male pseudohermaphrodites with the feminizing testes syndrome.

The role of the human testis in the production of 17beta-estradiol (E(2)) was investigated by determining the concentration of E(2) and testosterone in peripheral and spermatic vein plasma samples. Specimens were obtained from eight normal men, three men with hypogonadism, and two patients with the incomplete form of the feminizing testes syndrome. For comparison, similar studies were performed in four monkeys, 10 mongrel dogs, and 4 additional dogs who were given 1000 IU of human chorionic gonadotropin/day for 5 days. Plasma E(2) was measured by radioimmunoassay utilizing sheep anti-E(2) serum preceded by ether extraction and thin layer chromatographic separation of plasma steroids. Procedural blanks, which were subtracted from all reported values were 14.1+/-0.74 (SEM) pg for deionized water and 13.1+/-0.66 pg for charcoaladsorbed pooled male plasma. Pooled male and pooled female control plasmas averaged 17+/-0.71 pg/ml and 95+/-6.9 pg/ml, respectively; individual adult male specimens ranged between 8 and 28 with a mean of 18+/-1.4 pg/ml. In the eight normal men, the mean peripheral vein E(2) concentration was 20+/-1.6 pg/ml, while the spermatic vein concentration was 50 times as great, 1049+/-57 pg/ml. All three patients with testicular abnormalities had low spermatic vein E(2) concentrations (160, 280, and 416 pg/ml). Lesser E(2) gradients were found across the simian (3-fold) and canine (approximately 12-fold) testes. Testicular testosterone gradients (human 110-, simian 10-, and canine 77-fold) were greater than the E(2) gradients in all three species. In four dogs, HCG treatment elicited a 6-fold increase in peripheral and a 9-fold increase in spermatic vein testosterone concentrations; however, peripheral and spermatic vein E(2) concentrations did not differ from control values. Spermatic vein E(2) concentrations were > 4600 and 2210 pg/ml (post-HCG) in two patients with the incomplete form of the feminizing testes syndrome. Postorchiectomy, peripheral E(2) and testosterone concentrations fell precipitously in both patients, confirming the major contribution of the testes, in this syndrome, to circulating E(2) and testosterone. These studies provide direct evidence that the human testic secretes estradiol.

Adult↗

The effects of castration on adrenal testosterone secretion in men with prostatic carcinoma.

Selective adrenal vein catheterization was done on intact and castrated men with prostatic carcinoma. Adrenal to peripheral venous testosterone gradients were observed in all patients, indicating adrenal production of this hormone. No compensatory adrenal production of testosterone was noted during a 17-month period after orchiectomy. The data suggest that the human adrenal in castrates produces testosterone, which may explain why adrenal ablation can offer palliation in some patients with prostatic carcinoma.

Adrenal Glands↗

Testosterone secretion in the rat in response to chorionic gonadotrophin: alterations with age.

It has been reported by others that both prevailing blood concentrations of testosterone and Leydig cell response to gonadotrophin (up to 1 h after injection) are reduced in the aged male rat. Although resting levels of plasma testosterone in our aged (24-26 months old) Sprague-Dawley rat are also depressed compared with young (3-4 months) or mature (12 months) animals of the same strain, subcutaneous injection with human chorionic gonadotrophin for 3 days restores secretory function, producing testosterone levels indistinguishable from those of similarly stimulated younger rats. In short term experiments, old rats did show a diminished testesterone secretory response to human chorionic gonadotrophin 1 h after a single intravenous injection, consistent with previous reports, but restoration of normal stimulated levels was observed by 2 h, and persisted up to 24 h. These findings differ from the demonstrated intrinsic testicular hyporesponsiveness to gonadotrophin of aged men, and probably represented a state of chronic understimulation of the aged rat Leydig cells, due to low prevailing levels of LH.

Aging↗

A testosterone-secreting, gonadotropin-responsive pure thecoma and polycystic ovarian disease.

UNLABELLED: A 31-yr-old hirsute female with oligoamenorrhea since menarche had markedly elevated peripheral plasma testosterone (T) concentrations of 250-255 ng/100 ml (normal 20-60 ng/100 ml), which lacked a diurnal rhythm, were not suppressed by dexamethasone, were decreased by ACTH, and were massively increased to 2,530 ng/100 ml by human chorionic gonadotropin (hCG). The binding capacity of T-binding globulin (TeBG) was 0.2 mug/100 ml (normal = 1.1-3.3 mug/100 ml). Plasma delta 4-androstenedione (A) was elevated at 374-681 ng/100 ml (normal = 90-135 ng/100 ml). Plasma estrone (E1) and estradiol (E2) were normal. The endometrium was proliferative. A T-secreting tumor was suspected because the plasma T levels were higher than those observed in polycystic ovarian disease. Exploratory surgery revealed bilateral polycystic ovaries and a pure thecoma in the right ovary which was not visible on surface examination. The thecoma did not contain granulosa cells. Plasma T in the right ovarian vein, draining the tumor, was 28,200 ng/100 ml and in the left ovarian vein was 2,600 ng/100 ml. Plasma A was elevated in both ovarian veins: 11,170 ng/100 ml on the left and 8,360 ng/100 ml on the right. The thecoma contained 1.35 mug/g of T and only 0.014 mug/g and 0.007 mug/g of E2 and E1, respectively. Plasma A and T after bilateral oophorectomy and removal of the thecoma were normal at 184 ng/100 ml and 40 ng/100 ml, respectively. CONCLUSIONS: 1) This pure thecoma produced primarily T rather than E1 OR E2 and was gonadotropin-responsive. 2) A very high plasma androgen level in a female is an important clue to the presence of a tumor. A T-secreting tumor should be ssupected when the peripheral plasma T is over 250 ng/100 ml and when plasma T increases to over 1,000 ng/100 ml following hCG stimulation. 3) Tumors cannot be classified as estrogenic or androgenic on the basis of the character of the endometrium.

Adult↗

Testosterone-secreting gonadotropin-responsive adrenal adenoma and its treatment with the antiandrogen flutamide.

A 55-year-old woman with virilization had an appreciably elevated testosterone level, which was not suppressed by dexamethasone, but was increased by stimulation with human chorionic gonadotropin (hCG). Ultrasonography and computed tomography revealed an adenoma 2.5-3.0 cm in diameter in the right adrenal gland. The patient was treated with the antiandrogen flutamide in a daily dose of 500 mg for 4 months. A substantial regression of her hirsutism was observed during flutamide administration, but the serum testosterone level remained high. Right adrenalectomy was performed. Histologically, the tumor proved to be an adrenocortical adenoma of zona reticularis type. The adenoma tissue contained specific hCG receptors (187 fmol/g). The steroid concentration in the tumor tissue was examined by means of high pressure liquid chromatography-radioimmunoassay (HPLC-RIA). A significantly increased testosterone content was detected, and the levels of its precursors, androstenedione and dehydroepiandrosterone, were also elevated. Following adrenalectomy, serum testosterone concentration decreased to the normal level. The mechanism of the inappropriate regulation in the testosterone production of the adrenal tumor has not been fully elucidated.

Adenoma↗

The high-affinity non-peptide CRH1 receptor antagonist R121919 attenuates stress-induced alterations in plasma oxytocin, prolactin, and testosterone secretion in rats.

Evidence from basic and clinical research suggests that hyperactivity of central corticotropin-releasing hormone (CRH) circuits contributes to causality and course of affective disorders. Therefore, CRH receptor antagonists have attracted attention as potential therapeutics. We could previously show that the novel high-affinity non-peptide CRH 1 receptor antagonist R121919 significantly inhibits stress-induced corticotropin release and displays anxiolytic effects in rats selectively bred for high anxiety-related behavior. These animals are characterized by their innate hyper-reactivity of the hypothalamic-pituitary-adrenocortical system linked to an increased emotionality and therefore are suitable for the evaluation of CRH 1 receptor antagonists. Here we show that in addition to its effects on anxiety-related behavior and corticotropin secretion, R121919 attenuates the stress-induced release of corticosterone, prolactin, and oxytocin. Moreover, the decrease in plasma testosterone following exposure to stress is abolished by R121919. Our data indicate that antagonism of CRH 1 receptors may prevent stress-associated endocrine alterations.

Adrenocorticotropic Hormone↗

Ontogeny of gonadal luteinizing hormone and follicle-stimulating hormone receptors in the fetal pig and related changes in gonadotropin and testosterone secretion.

Fetuses of Large White and Meishan sows were collected at 28, 35, 49, 56, 75, 90, 103, and 113 days of gestation. LH, FSH, and testosterone concentrations were measured either in amniotic fluid (Days 28-56) or in arterial umbilical blood (Days 75-113). Gonads were analyzed for their content of LH and FSH receptors and RNA transcripts. Most of these parameters were similar in the two breeds, except that the mean testosterone concentration was higher (p < 0.05) in the plasma of 75-113-day Meishan fetuses (309 and 136 pg/ml in males and females, respectively) than in Large White fetuses (152 and 109 pg/ml). Higher testosterone concentrations were detected in males than in females, either in amniotic fluid (114 vs. 81 pg/ml, p < 0.05) or in plasma (230 vs. 122 pg/ml, p < 0.01). In contrast, higher gonadotropin concentrations were found in the plasma of females than in that of males (2 vs. 1.6 ng/ml LH and 4.2 vs. 1.4 ng/ml FSH, p < 0.05). In the testis, 2-3 pmol/g gonad of LH and FSH receptors were detected as early as Day 28. This value increased to 10-13 pmol/g between 35 and 56 days before declining to 3-5 pmol/g after Day 90. In ovaries, LH receptors were detected in the earlier period (Days 28-56) at 1-3 pmol/g before diminishing to 0.1-0.4 pmol/g. FSH receptors were higher at Day 28 (1 pmol/g) than at any subsequent stage (0.1-0.4 pmol/g). The gonadal content of RNA transcripts was significantly higher in testes than in ovaries.(ABSTRACT TRUNCATED AT 250 WORDS)

Amniotic Fluid↗