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PubMed1988

Immediate postnatal rise in whole body androgen content in male rats: correlation with increased testicular content and reduced body clearance of testosterone.

Whole body content of androgen (testosterone + 5 alpha-dihydrotestosterone) was invariably higher in male than in female rat pups killed 1 or 3 h after natural delivery, whereas androgen content was equivalent in males and females killed immediately or 6, 12, and 24 h after birth. Testicular content of androgen was significantly elevated in males killed 1 and 24 h after birth, compared with levels in males killed immediately, or 3, 6, and 12 h after birth. Thus, heightened testicular androgen content was only initially associated with increased systemic levels of androgen in males during the immediate postpartum period. A second study assessed the possibility that the body's clearance (i.e., metabolism plus excretion) of testosterone is lower in newborn rats upon separation from the placental circulation than in slightly older pups. Rats of both sexes killed 1 and 3 h after s.c. injection of [3H] testosterone had significantly higher plasma concentrations of [3H] testosterone as well as several 5 alpha-reduced androgens (5 alpha-dihydrotestosterone, 3 alpha-androstanediol, and androsterone) when injections were given within minutes as opposed to 24 h after birth. This suggests that in both sexes the clearance of testosterone is slower immediately after birth than at later ages. This phenomenon together with a brief postnatal elevation in the testicular synthesis and secretion of testosterone may explain the temporary rise in circulating androgen concentrations that occurs in the newborn male rat.

Age Factors↗
PubMed1989

Photoperiodic influences on sexual behavior in male Syrian hamsters.

The effect of photoperiodic conditions on sexual behavior was investigated in male Syrian hamsters that were either gonadally intact, or castrated and treated with low doses of testosterone throughout the experiment. Hamsters were exposed to long (LD 16:8) or short (LD 8:16) days for 7 weeks; for the next 8 weeks, either they were exposed to an intermediate daylength (LD 12:12), or daylength conditions remained unchanged. Sexual behavior was affected by photoperiod conditions in both gonadally intact animals and testosterone-treated castrates, but to different degrees. Intact males exposed to short days for 15 weeks exhibited gonadal regression, and their copulatory performance was impaired. The percentage of animals that intromitted or ejaculated was significantly reduced. Additional measures of sexual performance among the copulating males were also affected. In contrast, among the castrates with testosterone clamped at low but stable levels, the proportion of males that mounted, intromitted, or ejaculated was not affected by photoperiod. However, among the males that continued to copulate, sexual performance changes were present in the short-day castrates that resembled those displayed by the intact males. We infer that these behavioral effects in both hormonal conditions reflect primarily a difficulty in the attainment of intromission. Gonadal regression alone cannot easily account for the behavioral deficits of the intact males, because circulating testosterone levels at the end of the experiment were not significantly different between the gonadally intact hamsters and the castrated, testosterone-treated hamsters exposed continuously to short days. Males transferred from either long or short days to the intermediate-daylength condition responded behaviorally to this photoperiod as if it were a short day, that is, their ejaculatory frequency declined. We conclude that male hamsters exposed to photoinhibitory daylengths exhibit deficits in their sexual behavior, not only because endogenous levels of testosterone decrease, but also because the substrates on which this hormone acts become less responsive. We hypothesize that under physiological conditions, the episodic secretion of testosterone imposes constraints on the maintenance or restoration of copulation, and that the potent behavioral effects achieved by constant-release implants of testosterone may mask the presence of photoperiodically induced alterations in the hamster's sensitivity to this gonadal hormone.

Animals↗
PubMed1986

In vitro ovarian responses to pulsatile and continuous gonadotrophin administration on steroid secretion and oocyte maturation in the frogs, Rana pipiens and Rana catesbeiana.

An in vitro superfusion system was used to study the relative effects of pulsatile and continuous gonadotrophin administration on steroid secretion and oocyte maturation in Rana pipiens ovaries. Pulsatile (10 min pulse/hr) delivery of pituitary extract (PE) resulted in a slightly (insignificantly) lower level of testosterone (T) secretion over a 12-hr period. Administration of a fivefold lower, subliminal amount of PE instead of hormone-free media between pulses did not change the pattern of T secretion. When the interpulse frequency was increased to 2 or 3 hr, there were notable oscillations in T secretion which corresponded to the peaks in luteinizing hormone associated with the PE. In four experiments ovarian fragments underwent oocyte maturation, but this occurred only in fragments that received continuous PE stimulation. Progesterone (P) secretion was measurable only when oocyte maturation was observed in the ovarian fragment. Rana catesbeiana ovarian fragments exposed to continuous superfusion with homologous PE produced more T than those receiving hourly pulses of PE over a 6-hr period. Oocyte maturation accompanied by P secretion was observed in one experiment under continuous, but not pulsatile administration of PE. These results suggest that the frog ovary may be more resistant than the mammalian ovary to "down-regulation" under continuous gonadotrophic stimulation. The implications of these results on the frog pituitary--gonadal axis are discussed.

Animals↗
PubMed1992

Exposure to bleached kraft pulp mill effluent disrupts the pituitary-gonadal axis of white sucker at multiple sites.

Our recent studies have demonstrated reproductive problems in white sucker (Catostomus commersoni) exposed to bleached kraft pulp mill effluent (BKME) at Jackfish Bay on Lake Superior. These fish exhibit delayed sexual maturity, reduced gonadal size, reduced secondary sexual characteristics, and circulating steroid levels depressed relative to those of reference populations. The present studies were designed to evaluate sites in the pituitary-gonadal axis of prespawning white sucker affected by BKME exposure. At the time of entry to the spawning stream, plasma levels of immunoreactive gonadotropin (GtH)-II (LH-type GtH) in male and female white sucker were 30- and 50-fold lower, respectively, than the levels in fish from a reference site. A single intraperitoneal injection of D-Arg6, Pro9N-Et sGnRH (sGnRH-A, 0.1 mg/kg) increased plasma GtH levels in male and female fish at both sites, although the magnitude of the response was greatly reduced in BKME-exposed fish. Fish at the BKME site did not ovulate in response to sGnRH-A, while 10 of 10 fish from the reference site ovulated within 6 hr. Plasma 17 alpha,20 beta-dihydroxy-4-pregnen-3-one (17,20 beta-P) levels were depressed in BKME-exposed fish and unlike fish at the reference site, failed to increase in response to sGnRH-A. Testosterone levels in both sexes and 11-ketostestosterone levels in males were elevated in fish from the reference site but were not further increased by GnRH treatment. In contrast, BKME-exposed fish exhibit a transitory increase in testosterone levels in response to the GnRH analog. In vitro incubations of ovarian follicles obtained from fish at the BKME site revealed depressed basal secretion of testosterone and 17,20 beta-P and reduced responsiveness to the GtH analog human chorionic gonadotropin and to forskolin, a direct activator of adenylate cyclase. By comparison, ovarian follicles from fish collected at BKME and reference sites produced similar levels of prostaglandin E basally and in response to a phorbol ester and calcium ionophore A23187, suggesting that BKME effects on ovarian function are selective and do not reflect a general impairment of ovarian function. BKME-exposed fish had plasma levels of testosterone glucuronide proportionately lower than those of reference fish, suggesting that there are site differences in the peripheral metabolism of steroids. These studies demonstrate that BKME exposure affects reproduction by acting at multiple sites in the pituitary-gonadal axis.

Animals↗
PubMed1984

Testicular function and sexual activity in senescent mice.

The steroidogenic potentials of testes from 6-mo-old and approximately 28-mo-old CB6F1 mice were compared by measuring the secretion rate of 11 steroids produced by testes perfused in vitro. Testes from 6- and 28- to 30-mo-old mice secreted similar amounts of testosterone, but marked differences in the secretion of testosterone biosynthetic intermediates were discovered. Testes of old mice produced significantly more (P less than 0.01) delta 5-steroids than young male mouse testes. The presence or absence of sexual activity among old male mice was not correlated with changes in testicular steroidogenesis or plasma steroid levels. The results suggest that selected alterations in androgen biosynthesis occur during aging, but that the decline in reproductive performance among old mice is not attributable to deficits in testicular steroidogenesis. Rather, age-associated losses in sexual activity may be mediated by disturbances in the central nervous system.

Aging↗
PubMed1996

Incomplete gonadal dysgenesis.

A 21-year-old phenotypic male with ambiguous external genitalia and hypospadias was referred for cytogenetic studies. Exploratory laparotomy revealed presence of a small atropic uterus, unilateral gonadal dysgenesis with fallopian tubes on both sides and a cryptorchid testis on the left side. No gonad could be traced on the right side. Chromosomal analysis from peripheral whole blood culture revealed a 46,XY cell line. No mosaicism was detected. Endocrine studies showed elevated levels of serum FSH and LH with low borderline testosterone level and failure to respond to HCG stimulation. The presence of fallopian tube next to testis suggests absence of anti-Mullerian hormone secretion by Sertoli cells. The absence of Wolffian duct derivatives indicates insufficient secretion of testosterone by Leydig cells.

Adult↗
PubMed1978

Effects of high altitude on plasma concentrations of testosterone and pituitary gonadotropins in man.

Ten healthy male volunteers were rapidly taken to the top of Pike's Peak, altitude 14,100 ft (4,300 m) where they remained at the research station for 6 d. There were no significant changes, compared to their values at sea-level, in the plasma concentrations of testosterone, FSH, and LH during this period. There was a highly significant direct correlation between individual changes in testosterone and the gonadotropins on Day 1. Our data provide no evidence for an acute effect of high-altitude per se on the secretion of testosterone and the pituitary gonadotropins.

Adult↗
PubMed1990

[Study of secretion and blood protein transport of testosterone in patients with neurogenic facial diseases].

Altogether 85 patients with the painful syndromes in the facial and head areas were examined for secretion and transport of testosterone, the main androgen occurring in the body of adult man, by the blood proteins globulin- and albumin-binding sex steroids. All the women examined were in the menopause. The majority of the patients manifested hyperandrogenemia: a decrease in the concentration of sex steroids-binding globulin, rise of total testosterone and its free fraction in the blood serum as well as increase of the index of free androgens. Approaches to the correction of the revealed abnormalities and the role played by those abnormalities in the pathogenesis of the above-indicated diseases are under discussion.

Adult↗
PubMed2004

Lack of spermatotoxic effects of methyl and ethyl esters of p-hydroxybenzoic acid in rats.

Parabens are alkyl esters of p-hydroxybenzoic acid widely used as preservatives in foodstuffs, cosmetics toiletries and pharmaceuticals. These compounds are known to exert a weak estrogenic activity in estrogen receptor assays in vitro. In addition butyl and propyl parabens show uterotrophic activity in vivo. It was previously shown that exposure of post-weaning rats and mice to butyl or propyl parabens adversely affects the secretion of testosterone and the function of the male reproductive system. In the present study, it is shown that methyl and ethyl parabens do not adversely affect the secretion of sex hormones or the male reproductive function. Methyl and ethyl parabens were administered to 25-27-day-old rats assigned to five groups of eight animals each, at doses of 0.1% and 1.0% each in the rat's diet. At the end of 8 weeks, the rats were sacrificed by decapitation and the weights of the testes, epididymides, prostates, seminal vesicles and preputial glands were determined. There were no treatment-related effects of either compound on the organ weights in any of the study groups. Neither compound exhibited anti-spermatogenic effects nor elicited changes in levels of testosterone, LH and FSH at a dose level of about 1000 mg/kg of body weight per day.

Animals↗
PubMed1998

The time course of follicle-stimulating hormone suppression by recombinant human inhibin A in the adult male rhesus monkey (Macaca mulatta).

In higher primates, FSH secretion appears to be regulated by a control system consistent with that described by the classical inhibin hypothesis. The purpose of the present experiment was to examine the time course of inhibin's action to suppress FSH secretion in the intact adult male rhesus monkey. To this end, five adult males implanted with indwelling venous catheters and exhibiting typical episodic patterns of LH and testosterone (T) secretion received a 4-day i.v. infusion of recombinant human (rh) inhibin A (832 ng/h x kg) followed, after a 4-week interval, by vehicle infusion of similar duration. Changes in circulating FSH concentrations during the inhibin and vehicle infusions were determined using a sensitive homologous macaque RIA, whereas enzyme-linked immunosorbent assays were employed to track inhibin A, inhibin B, and inhibin pro-alpha-C levels during the experiment. Normal pulsatile activity in the hypothalamic-pituitary-Leydig cell axis was confirmed by monitoring changes in circulating concentrations of LH and T in 12-h windows of sequential blood collection (1200-2400 h; every 20 min) before, during, and after the rh inhibin A and vehicle infusions. Although infusion of rh inhibin A, which led to a 12 ng/ml square wave increment in circulating levels of this inhibin dimer, produced a marked decline in circulating FSH concentrations, significant suppression of the secretion of this gonadotropin was not manifest until 54 h after initiation of the infusion. Despite the marked decline in FSH secretion during the last 24 h of the 4-day infusion of recombinant hormone, circulating inhibin B and pro-alpha-C concentrations were maintained at preinfusion control levels (1 ng/ml). The finding that imposition of an exaggerated circulating inhibin signal led to suppression of FSH secretion in the male monkey only after 2 days of exposure to the hormone indicates that in this species the feedback action of testicular inhibin on FSH secretion is heavily lagged. Moreover, as the decrease in FSH did not lead to changes in native inhibin secretion, it seems reasonable to propose that the FSH-inhibin feedback loop that governs testicular function in higher primates operates with considerable hysteresis at both the pituitary and gonadal levels. The failure of dramatically elevated inhibin A levels to influence the pulsatile secretion of LH in the monkey reinforces the idea that in this species the pituitary action of testicular inhibin is specific for FSH and does not involve modulation of GnRH receptor levels.

Animals↗
PubMedDate not supplied

Testicular activity in mice selected for increased body weight.

Parameters of testicular function were studied in mice selected for increased body weight and in contemporaneous unselected controls. Spermatogenesis occurred at the same time in the two lines. Body weight, testis weight, mean seminiferous tubular diameter and serum testosterone were increased significantly in the high growth mice. It is suggested that some genetically determined differences in body size are brought about by the differential secretion of testosterone.

Age Factors↗
PubMed1983

Sexual development, maturation, and behavior.

The Y chromosome directs the primitive gonad to develop into a testis. Without a Y chromosome an ovary will develop, but that ovary will not be normal unless two X chromosomes are present. Active intervention is needed for male differentiation; internal male structures will not be found unless sufficient and effective testosterone is secreted by the immature testis to develop the wolffian duct system into the internal male reproductive tract. The testis must also secrete mullerian regression factor to cause the demise of the internal female duct structures. Finally, enough 5-alpha-reductase activity must be present to convert testosterone into dihydrotestosterone for the normal virilization of the male external genitalia. Without testosterone or its receptor sites, without dihydrotestosterone, and without mullerian regression factor, the reproductive system is female. Early in life, a child assumes both a gender identity (an awareness of what sex he or she belongs to) and a gender role (behavior deemed to be more or less characteristic of one sex or the other). As puberty is passed, sexual orientation becomes more obvious, although the development of that orientation has probably been in the making since early childhood. Early developmental hormone milieu and social environment undoubtedly all play a role in subsequent sexual behavioral patterns, but the extent to which each of these impacts upon that behavior still remains unknown.

Adolescent↗
PubMed1991

Determination of prostatic secretion in rats: effect of neurotransmitters and testosterone.

To study the neuronal and hormonal control of prostatic secretion, the prostatic urethra was cannulated in urethane anesthetized rats. The volume of prostatic secretion was measured following infusion of cholinergic and adrenergic agonists intact animals. Prostatic secretion was elicited by norepinephrine, phenylephrine and carbachol; but not by clonidine, isoproterenol, pilocarpine, or acetylcholine. Phenylephrine and norepinephrine infusions caused a high initial rate of secretion, which then declined rapidly. Carbachol infusion, in contrast, produced a low but constant rate of secretion that was maintained for up to 1 hour. Histological examination of the prostate revealed contraction of smooth muscle surrounding prostatic ducts after infusion of phenylephrine and norepinephrine, but not carbachol. Prostatic secretion was also measured in castrated rats supplemented with various doses of testosterone. Testosterone exerted a dose dependent control of prostatic weight and secretory volume. These results indicate 1) alpha 1 receptor agonists can cause contraction of smooth muscle to expel fluid from the rat prostate, 2) carbachol induces prostatic secretion through a mechanism other than contraction of gland, and 3) testosterone has a primary role in controlling prostatic size.

Acetylcholine↗
PubMed1984

Pituitary gonadotropin-releasing hormone (GnRH) receptor responses to GnRH in hypothalamus-lesioned rats: inhibition of responses by hyperprolactinemia and evidence that testosterone and estradiol modulate gonadotropin secretion at postreceptor sites.

Increased hypothalamic GnRH secretion appears to influence positively the number of pituitary GnRH receptors (GnRH-R). GnRH-R increase after castration in male rats, and this rise can be prevented by testosterone (T), anti-GnRH sera, or hypothalamic lesions. GnRH also increases serum LH and GnRH-R in hypothalamus-lesioned rats, and these animals injected with exogenous GnRH are, therefore, a good model in which to study the site of steroid feedback at the pituitary level. Adult male and female rats were gonadectomized, and radiofrequency lesions were placed in the hypothalamus. Males received T implants, and females received estradiol implants at the time of surgery. Empty capsules were placed in the control animals. Beginning 3-5 days later, animals in each group were injected every 8 h with vehicle (BSA) or GnRH (0.002-200 micrograms/day) for 2 days. After these GnRH injections, all rats received 6.6 micrograms GnRH, sc, 1 h before decapitation to determine acute LH and FSH responses. GnRH-R were determined by saturation analysis using 125I-D-Ala6-GnRH ethylamide as ligand. In males, GnRH injections increased GnRH-R. T inhibited acute LH and FSH responses to GnRH in all groups, but had little effect on GnRH-R, indicating that T inhibits gonadotropin secretion at a post-GnRH receptor site. In females, the GnRH-R response to GnRH was less marked, and only the 200 micrograms/day dose of GnRH increased GnRH-R, indicating that the positive feedback effects of estradiol at the pituitary level are also exerted at a site distal to the GnRH receptor. There was no positive correlation between the number of GnRH-R and GnRH-stimulated gonadotropin release in males or females. Female rats with hypothalamic lesions had markedly elevated serum PRL levels (greater than 300 ng/ml). Suppression of PRL secretion by bromocryptine resulted in augmented GnRH-R responses to GnRH, and GnRH-R concentrations rose to the same values induced in males. This suggests that hyperprolactinemia inhibits GnRH-R responses to GnRH in females by a direct action on the pituitary gonadotroph.

Animals↗
PubMed1981

The role of gonadotropins and testosterone in progesterone production by human ovarian granulosa cells.

Granulosa and theca cells obtained from patients were isolated and cultivated in a chemically defined medium containing gonadotropins and/or testosterone. Progesterone secretion by granulosa cells was consistently stimulated (2-40-fold) in all 5 patients by the addition of follicle-stimulating hormone (FSH, 0.25 micrograms/ml). In the presence of testosterone (0.5 micro M) alone, progesterone production was stimulated (2-8-fold) in 4 out of the 5 patients and cells of one patient showed a greater response to testosterone than to FSH alone. In 2 of the 5 patients, it was also noted that FSH and testosterone acted in a synergistic manner to stimulate the production of progesterone by granulosa cells. On the other hand, human chorionic gonadotropin (hCG, 1.0 IU/ml) alone failed to exert any significant effect. None of the treatments examined altered the production of progesterone by theca cells. These results suggest a role for FSH and testosterone in regulating progesterone biosynthesis by granulosa cells of the human ovary during follicular development.

Adult↗
PubMed2005

Testosterone supplementation in healthy older men drives GH and IGF-I secretion without potentiating peptidyl secretagogue efficacy.

OBJECTIVE: Testosterone supplementation increases GH and IGF-I concentrations in healthy older men via unknown mechanisms. We examine the hypotheses that (i) testosterone amplifies stimulation of GH secretion by GH-releasing peptide (GHRP)-2 or GH-releasing hormone (GHRH) infused with l-arginine to limit somatostatin outflow (i.e. upregulates each agonistic pathway), (ii) testosterone augments the effect of both peptidyl secretagogues infused together (i.e. reduces opposition by hypothalamic somatostatin) and (iii) abdominal visceral fat (AVF) mass is a negative determinant of specific secretagogue-stimulated GH secretion. DESIGN: Randomized double-blind crossover design of placebo versus testosterone administration in healthy older men. METHODS: Deconvolution analysis was used to estimate basal GH secretion and the mass (integral) and waveform (time-shape) of GH secretory bursts. RESULTS: Statistical contrasts revealed that administration of testosterone compared with placebo in seven men aged 60-77 years increased fasting concentrations of GH (P < 0.01) and IGF-I (P = 0.003), and basal (P < 0.005) and pulsatile (P < 0.01) GH secretion. Testosterone did not alter the absolute value or rank order of secretagogue efficacy: l-arginine/GHRP-2 (23-fold effect over saline) = GHRH/GHRP-2 (20-fold) > l-arginine/GHRH (7.5-fold). Waveform reconstruction indicated that each stimulus pair accelerated initial GH secretion within a burst (P < 0.01). Regression analysis disclosed a significant inverse association between GH secretory-burst mass and computer tomography-estimated AVF following stimulation with l-arginine/GHRH after testosterone supplementation (R(2) = 0.54, P = 0.015). CONCLUSION: Supraphysiological testosterone concentrations augment GH and IGF-I production in the elderly male without altering maximal somatotrope responses to single and combined GHRH and GHRP-2 drive, thus predicting multifactorial mechanisms of testosterone upregulation.

Adipose Tissue↗