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Testosterone levels of free-ranging resident mantled howler monkey males in relation to the number and density of solitary males: a test of the challenge hypothesis.

The challenge hypothesis asserts that testosterone levels and aggression in male adult animals are closely associated with one another in the context of intense reproductive competition, particularly when males challenge one another for the access to females. For mantled howler monkeys (Alouatta palliata), the presence of a solitary male in the vicinity of a social group can be considered a threat for the reproductive success of the resident males, as group takeovers by solitary males are followed by a reestablishment of the access to females among group males and sometimes by infanticide. Therefore, these episodes should be accompanied by an increase in testosterone secretion according to the challenge hypothesis. In order to test our prediction, we relate different group and subpopulation variables to the testosterone levels measured in feces collected from 10 groups living in 6 forest fragments, at Los Tuxtlas, Mexico. Our results suggest that resident A. palliata males regard solitary individuals as potential contesters for their reproductive success and that they respond to interactions with them with an increase in testosterone levels, that is increasing their aggressiveness. Our results also suggest that in the studied groups all males have at least certain access to mates and that the entrance of a new male would affect their reproductive success negatively. Finally, the negative effects of chronically high testosterone levels may be negatively affecting the fitness of our study groups living in high population densities and small fragments.

Alouatta↗

Pharmacokinetics of new testosterone transdermal therapeutic systems in gonadotropin-releasing hormone antagonist-suppressed normal men.

In a phase I single-center, open, randomized pilot study with a three-way cross-over design the pharmacokinetics of three testosterone-containing transdermal therapeutic systems were evaluated in healthy male volunteers. Testosterone TTS HEXAL type 1 and 2 are nonscrotal membrane patches differing in the kind of adhesive used. 6 subjects were treated with low dose Testosterone TTS type 1, high dose Testosterone TTS type 1 and low dose Testosterone TTS type 2. To eliminate the influence of endogenous serum testosterone, the endogenous testosterone secretion was suppressed by the GnRH antagonist cetrorelix. In all subjects under GnRH antagonist treatment a marked suppression of LH, FSH, testosterone, DHT and estradiol was observed. Physiologic testosterone levels were achieved during the 24-hour-application period. Maximal serum levels were reached after 4 hours with both TTS systems. Both systems appear suited for further testing because both enable a physiological circadian profile to be achieved. GnRH-antagonist pretreatment is a useful model to evaluate the effect of exogenous testosterone in clinical studies, when, due to fluctuations in endogenous hormone levels, an estimation of the proportion of exogenous steroid is not possible.

Administration, Cutaneous↗

[Hypothalamo-pituitary-testicular function in male Japanese monkeys (Macaca fuscata) in non-mating season].

We examined seasonal changes in serum testosterone and LH, and investigated mechanisms of reduction of testicular function in non-mating season in male Japanese monkeys. Blood samples were collected monthly throughout one year in 5 males, and hCG and LH-RH were administered to 5 and 3 animals, respectively, in non-mating and mating season. Serum testosterone and LH were measured by RIA. Serum testosterone showed the obvious seasonal changes, being low in March to August and high in October to February. Also we found the seasonal changes in LH being low in May to August and high in September to February. When hCG was administered to 5 monkeys in mating season (January), serum testosterone levels increased markedly 30 to 180 min after single administration and showed further increases after continuous administrations for four days. However, in non-mating season (August), serum testosterone showed a little increase for the same treatment as in mating season. These data showed that the reserve ability of testosterone secretion in testis in non-mating season decreased obviously in contrast to mating season. The increase of serum LH and testosterone levels in 3 males in non-mating season (July) after LH-RH single administration were less than those in mating season (December). In intermediate period (September) between non-mating season and mating season, LH showed higher level than that in mating season but the testosterone level was the same extent as in non-mating season.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Relationships among intramuscular collagen, serum hydroxyproline and serum testosterone in growing rams and wethers.

Concentration and maturation of collagen and serum concentrations of hydroxyproline and testosterone were determined in growing rams and wethers to characterize developmental changes in collagen associated with a representative testicular steroid. Groups of eight rams and eight wethers were slaughtered at 12, 18, 24 and 30 wk of age. Concentrations of collagen in longissimus, supraspinatus and infraspinatus muscles and serum hydroxyproline were greater (P less than .05) in rams than in wethers at all ages. Collagen stability, as measured by collagen solubility and thermal shrinkage temperature, was greater (P less than .05) in wethers than in rams. Differences in collagen stability and serum hydroxyproline concentration indicated that collagen synthesis and turnover were more rapid in rams than in wethers. Serum hydroxyproline decreased (P less than .05) and collagen solubility decreased (P less than .05) with age, indicating that collagen turnover was occurring most rapidly in 12-wk-old lambs and that collagen maturation was predominant in 24- to 30-wk old lambs. Testosterone parameters measured in rams were unrelated within groups to collagen characteristics, possibly reflecting the high variability in testosterone secretion and the slow development of collagen. However, rams as young as 12 wk of age were under the influence of testosterone, and differences in collagen between rams and wethers were apparent at that time.

Animals↗

[Adverse effects of nonylphenol on the reproductive function of adult male SD rats].

OBJECTIVE: To assess the adverse effects of both in vivo and in vitro exposure to nonylphenol on the reproductive function of adult male SD rats. METHODS: Adult male SD rats were sacrificed after they had received oral nonylphenol at 50, 100, 200 mg/kg for 28 days. Both indications related to their reproductive function and histopathological section of testis were analyzed. In vitro study of testicular cells from adult male rats by use of culture solution with different nonylphenol concentrations was conducted. Testosterone production in cell culture medium was examined and the ultrastructure of Leydig cell, Sertoli cell and spermatogenesis cell were observed under electron microscope. RESULTS: In vivo study of the experiment animals in comparison with the controls revealed that sperm count and motility in testis of adult rats exposed to nonylphenol at doses of 100 mg/kg and above were significantly decreased, and the histopathological sections of testis showed atrophied seminiferous tubules and decreased spermatogenesis. In vitro study of testicular cell culture showed that testosterone secretion was inhibited. And electron microscopy disclosed that the endoplasmic reticulum of Leydig cell swelled, which might indicate the reduction of testosterone biosynthesis. CONCLUSION: Nonylphenol at higher dose directly impairs the reproductive function of adult male SD rats.

Animals↗

[A comparative in vitro culture study of the action of the chick embryo testis and testosterone on different target organs (author's transl)].

This is a survey of previously published data and some new ones. The target organs studied were chick and mouse wolffian ducts and mullerian ducts. The following statements can be made: 1. The anti-mullerian hormone of the chick embryo testis is active on both the avian and mammalian mullerian ducts. Testosterone on the contrary will stimulate them. 2. Testosterone will stimulate both the avian and mammalian wolffian ducts, the chick embryo testis will not. It is concluded that there is no testosterone secretion by the chick embryo testis or in too low a quantity to be effective. Thus, the chick embryo testis and testosterone exert quite different actions on all four target organs studied.

Animals↗

Sex differences in the development of estrogen receptors in the rat brain.

The mechanisms involved in sexual differentiation of the brain remain incompletely defined. In mammals, testosterone secretion by the male during early development permanently alters the capacity of the brain to respond to circulating estrogen. In rats, this change in estrogen responsiveness is associated with a reduction in estrogen receptor (ER) levels in the periventricular region of the preoptic area (PVP), the medial preoptic nucleus (MPO), and the hypothalamic ventromedial nucleus (VMN) of the male. To determine whether these differences represent a response to early testosterone exposure or a secondary consequence of gonadal secretions at puberty, ER levels were measured by quantitative in vitro autoradiography in the brains of rats killed at intervals between 1-10 and 28-49 days of age. As early as 24 hr after birth, ER sex differences in the MPO and PVP are already quantitatively similar to those observed in adulthood. A sex difference in the VMN emerges later, between 5 and 10 days of age. Differences between brain regions are also observed in the rate of ER development after the first week of life, ER concentrations in the PVP and MPO being close to adult levels within 1 day of birth, in contrast to the VMN where they increase markedly between Day 10 and adulthood in both sexes. These observations suggest that changes in ER concentrations may be one of the earliest hallmarks of brain sexual differentiation. Sex differences in ER in different brain regions may, however, be expressed asynchronously, providing a possible mechanism for variation in the duration of "critical periods" for testosterone-mediated organization of specific CNS functions.

Animals↗

Pharmacokinetics of a novel testosterone matrix transdermal system in healthy, premenopausal women and women infected with the human immunodeficiency virus.

The clinical consequences of androgen deficiency in human immunodeficiency virus (HIV)-infected women remain underappreciated. The pharmacokinetics of transdermally administered testosterone in premenopausal women and HIV-infected women have not been studied. In this study we compared the pharmacokinetics of a novel testosterone matrix transdermal system (TMTDS) in healthy premenopausal women and women infected with HIV. Eight menstruating HIV-infected women, 18-50 yr of age, who had been receiving stable antiretroviral therapy, including a protease inhibitor, for at least 12 weeks and nine healthy, menstruating women of comparable age were enrolled. After baseline sampling during a 24-h control period in the early follicular phase (days 1-6), two TMTDS patches were applied with an expected delivery rate of 300 microg testosterone daily over an application period of 3-4 days. After 72 h, the patches were removed, a second set of two patches was applied, and blood samples were drawn over 96 h. Baseline serum total and free testosterone levels were lower in HIV-infected women than in healthy women. A diurnal rhythm of testosterone secretion, with higher levels in the morning and lower levels in the late afternoon, was apparent in both groups of women. Free testosterone levels were in the midnormal range at baseline in healthy women and increased above the upper limit of normal during TMTDS application. In HIV-infected women, free testosterone levels were in the low normal range at baseline and rose into the upper normal range during patch application. Serum total testosterone levels increased into the midnormal range in HIV-infected women and into the upper normal range in healthy women during patch application. The mean increments in free and total testosterone levels were significantly lower in HIV-infected women than in healthy women. Testosterone bioavailability, expressed as the mean +/- SEM baseline-subtracted area under the total testosterone curve, was significantly greater in healthy women than in HIV-infected women [3323 +/- 566 ng/dL x h (115 +/- 20 nmol/L x h) vs. 1506 +/- 316 ng/dL x h (52 +/- 11 nmol/ L x h); P = 0.016]. Assuming a daily testosterone delivery rate of 300 microg/day, the apparent plasma clearance was significantly higher in HIV-infected women than in healthy women (2531 +/- 469 vs. 1127 +/- 217 L/day1 P = 0.022), respectively. There was no significant change from baseline in serum LH, sex hormone-binding globulin, and estradiol levels in either group. Serum FSH levels showed a greater decrease from baseline in healthy women. A regimen of two testosterone patches applied twice a week can maintain serum total and free testosterone levels in the mid- to upper normal range, respectively, in HIV-infected women with low testosterone levels. During TMTDS application, the increments in serum total and free testosterone levels are lower in HIV-infected women than in healthy women, presumably due to increased plasma clearance or decreased absorption. Further studies are needed to assess the effects of physiological androgen replacement in HIV-infected women.

Administration, Cutaneous↗

Relationships between plasma progesterone levels and testicular testosterone production in the rat fetus: effects of maternal ovariectomy.

The present study was performed to examine whether circulating progesterone regulates testicular testosterone production in the fetal rat. Progesterone levels in fetal plasma were found to increase from day 14.5 to day 16.5; thereafter they reached a plateau between days 16.5 and 18.5 (80 nmol/l) and decreased threefold between days 18.5 and 21.5. The addition of progesterone, within the range of normal plasma concentrations, induced a dose-dependent increase in testosterone produced in vitro by the testes on days 16.5 and 18.5 but not on day 20.5. However, in 18.5-day-old fetuses, individual plasma progesterone levels were not correlated with testicular testosterone production in vivo and in vitro. Furthermore, maternal bilateral ovariectomy induced a significant fall in plasma progesterone in 18.5-day-old fetuses; this was not associated with a reduction in plasma testosterone nor in testicular testosterone content, although the amount of testosterone secreted by the testis incubated in vitro was slightly but significantly reduced. It is concluded that circulating progesterone does not regulate testicular testosterone production in vivo although the testis may use plasma progesterone as a substrate. On day 18.5 after maternal ovariectomy, the decrease in plasma progesterone levels was similar in fetuses and mothers, suggesting that most fetal progesterone originates from maternal plasma.

Animals↗

The effect of neonatal vasectomy on testicular function.

The effect of unilateral or bilateral vasectomy on testicular weight and basal testosterone production in vitro was studied in neonatal intact and hemicastrated rats. Five days after right-side vasectomy ipsilateral to vasectomy testicular weight increased, and basal testosterone production decreased. Ten days postvasectomy the changes were opposite, and affected both testes. In hemicastrated animals hemivasectomy did not interfere with compensatory hypertrophy but induced a significant decrease in basal testosterone production. The data of the present study suggest that in neonatal animals intact ductus deferens bundle(s) is also required for the full control of testicular weight and basal testosterone secretion.

Animals↗

Does 1,25-dihydroxyvitamin D participate in the regulation of hormone release from endocrine glands?

The presence of receptors for 1,25-dihydroxyvitamin D3 in the pituitary, pancreas, testis, and ovary has raised the question of a possible direct role for 1,25-dihydroxyvitamin D (1,25(OH)2D) in the regulation of hormone synthesis and secretion. To evaluate this problem, six children with the syndrome of resistance to 1,25(OH)2D with rickets and alopecia underwent dynamic tests of insulin, TSH, PRL, GH, and testosterone secretion. Oral glucose loading resulted in normal glucose curves, subnormal peak insulin responses of 12-20 microU/ml in three hypocalcemic patients, and normal peak serum insulin values of 30-40 microU/ml in two normocalcemic patients. Basal serum, TSH, PRL, T4, and T3 concentrations were normal in all patients. Peak serum TSH values after TRH were 11-17 and 16-32 microU/ml in the hypo- and normocalcemic patients, respectively. The PRL response to TRH stimulation in either hypocalcemic or normocalcemic patients was normal [mean 26.2 +/- 5.1 (SD) ng/ml]. Peak serum GH levels were greater than 8 ng/ml in all five patients studied after one or more of the various stimuli. Serum testosterone concentrations after hCG stimulation were normal in the three patients studied (4.1-8.0 ng/ml). Thus, in children with resistance to 1,25(OH)2D, we could find no significant abnormalities in hormone secretion from the pituitary, pancreas, and testis apart from those presumably due to the hypocalcemia itself.

Calcitriol↗

In vitro effects of substance P and arginine-vasopressin on testosterone production in Leydig cells of short and long photoperiodic hamsters.

The aim of the present study was to determine the interaction between substance P (SP) and arginine-vasopressin (AVP) on basal and LH-stimulated testosterone production by Leydig cells isolated from hamsters kept under long or short days (LD-hamsters, SD-hamsters, respectively). SP inhibited the testosterone production of Leydig cells, its effect being more pronounced in the case of LH-stimulated steroidogenesis in LD-hamsters. Similarly, the addition of AVP to the culture medium resulted in a diminution of basal, as well as LH-stimulated testosterone secretions. When Leydig cells were co-incubated with SP (10(-7) M) and AVP (10(-7) M), a strong inhibition of the testosterone production by 50-60% was established in LD-animals. However, even within the experimental circumstances in SD-hamsters, the modulation of testosterone production by SP and AVP was evident. The reported results suggest that there is an interference of two regulatory pathways, namely photoperiodic dependence and paracrine control of testicular steroidogenesis in hamsters.

Animals↗

Lack of prenatal testosterone surge in fetal rats exposed to alcohol: alterations in testicular morphology and physiology.

Pregnant Sprague-Dawley rats were administered a liquid alcohol diet (35% ethanol-derived calories), a pair-fed isocaloric diet, or dry food pellets beginning on Day 14 of gestation and continuing until parturition. Testosterone levels in male fetuses were measured on Days 17 through 20 of gestation. The normal surge of testosterone on Days 18 and 19 was present in controls, but notably absent in male fetuses exposed to alcohol. Light microscopic examination of the testes at birth revealed a reduction in the number of leydig cells in the alcohol exposed group and the presence of a large number of vacuoles in the seminiferous tubules. In vitro studies of fetal testes at 18 and 22 days of gestation revealed that this in utero alcohol exposure regimen produced a marked insensitivity to rat LH (10 ng/ml) stimulation of testosterone secretion compared to controls. The response to ethanol (160 mg/dl) in alcohol exposed testes was characterized by a long-lasting suppression of testosterone compared to a large increase observed in control testes. No differences in anogenital distance were observed among the groups. Together, these data may explain some of the long-term feminizing and demasculinizing effects on reproductive and nonreproductive sexually dimorphic behaviors observed in adult males prenatally exposed to alcohol.

Anal Canal↗

LH and testosterone responses to GnRH in red deer (Cervus elaphus) stags kept in a manipulated photoperiod.

Six red deer stags from age 4 months were kept in a light-proof room under an artificial photoperiod consisting of 5.5 cycles of alternate 2-month periods of 16 h light and 8 h dark (16L:8D) and 8L:16D. At 2 or 3 weekly intervals from 10 months of age through 4 cycles, the stags were anaesthetized with xylazine and challenged i.v. with 10 micrograms GnRH. Blood samples were withdrawn immediately before and 10 and 60 min after injection. LH and testosterone concentrations were measured in all samples by RIA. Antler status was recorded daily. Peak LH values on each sampling day occurred in the sample taken 10 min after GnRH stimulation while peak testosterone occurred in the sample taken at 60 min. There were 4 cycles of LH and testosterone secretion accompanied by 4 antler cycles in the stags. The highest LH responses were detected during short days (8L:16D), and the highest testosterone responses were detected around the time of the change from short to long days. The responses of both hormones were lowest at the end of periods of long days or the beginning of short days. The increased pituitary LH response to GnRH was evident 4 weeks after the change to short days which are stimulatory for gonadal development. Antler casting occurred at the end of long days and cleaning at the end of short days. It is considered that antler cycles were due to the ability of the stags to vary release of LH and testosterone in response to changes in the artificial photoperiod.

Animals↗

Sex hormone status of the postmenopausal woman.

Plasma levels of testosterone, androstenedione, dehydroepiandrosterone and its sulphate, and of androstenediol, as well as estrone and estradiol, were determined in several groups of postmenopausal women. The ovaries contribute to plasma estrogen levels only early in the postmenopause, but continue to secrete testosterone and minimal amounts of androstenedione throughout the postmenopause. With age there is a decreased secretion by the adrenal of dehydroepiandrosterone (sulphate) and of androstenediol. The levels of androstenedione and estrone and the androstenedione/estrone ratio remain unchanged with increasing age. The levels of estrone and estradiol, and the ratios, estrone/androstenedione and estradiol/testosterone, are correlated with fat mass. There is also an inverse curvilinear relationship with precursor concentration. This suggests either a progressive saturation of the tissular aromatase with increasing percursor level, or the existence of an unknown estrogen precursor.

Adult↗

Appraising the instantaneous secretory rates of luteinizing hormone and testosterone in response to selective mu opiate receptor blockade in late pubertal boys.

The pulsatile properties of gonadotropin and testosterone release were examined before and after chronic mu opiate receptor blockade with naltrexone, 50 mg every other day, in four normal boys in late puberty (ages 14 8/12 to 15 1/12 years). The nature of spontaneous secretory events was appraised for immunoactive LH and testosterone in blood withdrawn every 20 minutes for 24 hours, using a novel, discrete deconvolution algorithm to estimate apparent instantaneous secretory rates. The application of this methodology revealed that the frequency of discrete LH instantaneous secretory rates increased after mu opiate receptor blockade (P = 0.011). More strikingly, all parameters of testosterone secretory events responded significantly to mu opiate receptor blockade, including increases in mean estimated secretory rate (+47%, P = 0.02), testosterone pulse frequency (+ 64%, P less than 0.001) and amplitude (+ 20%, P = 0.027). Correspondingly, decreases in testosterone interpulse secretory intervals (-35%, P = 0.001), secretory pulse duration (-19%, P = 0.042) and interpulse valley duration (-35%, P = 0.006) also were noted. There was a prominent diurnal rhythm in testosterone secretion with maximal values in the morning and late evening, and marked reductions in the afternoon, sometimes to prepubertal levels. This variation in the testosterone secretory profile paralleled that of LH. In response to naltrexone, the FSH concentration series showed a significant increase in the mean FSH concentration (+ 18%) P = 0.003) and mean peak amplitude (+ 15%, P = 0.002). These data provide indirect evidence of functional coupling of the opiate system with the hypothalamic GnRH pulse generator.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Ghrelin and reproduction: a novel signal linking energy status and fertility?

Ghrelin was originally identified in 1999 as the endogenous ligand of the growth hormone (GH) secretagogue receptor (GHS-R). Since then, an ever growing number of publications have reported the potential involvement of this molecule in the regulation of a large array of endocrine and non-endocrine functions, including the control of GH secretion and several other neuroendocrine axes as well as food intake and energy balance. On the basis of its proposed role as indicator of energy insufficiency and the proven reproductive effects of other regulators of energy homeostasis and growth (such as the adipocyte-derived hormone leptin), it is tempting to hypothesize that ghrelin might play a role in the control of reproductive function and fertility. Indeed, although evidences in this area are still fragmentary, we review herein data from different research groups, which have recently substantiated the reproductive facets of this newly identified hormone. Thus, expression of ghrelin has been demonstrated in human and rodent placenta, and ghrelin has been reported to inhibit early embryo development. In addition, ghrelin was shown to suppress luteinizing hormone (LH) secretion in vivo, and to decrease LH responsiveness to LH-releasing hormone (LHRH) in vitro. Moreover, ghrelin was able to inhibit stimulated testicular testosterone secretion, whereas androgens have been proven independent modulators of circulating ghrelin levels. In this context, our group has recently provided extensive evidence for the expression of ghrelin and its putative receptor, the type 1a GHS-R, in rat and human gonads. Testicular expression of ghrelin was highly selective for mature Leydig cells and under the hormonal control of pituitary LH, while in the ovary, expression of ghrelin was demonstrated in steroidogenically active luteal cells and interstitial hilus cells. Likewise, expression of GHS-R type 1a was demonstrated in Sertoli and Leydig cells of the testis and follicular, luteal and interstitial hilus cells in the ovary. In summary, the data so far available indicate that ghrelin may operate at different levels of the reproductive system, including the testis and the ovary, which are potential targets for systemic ghrelin actions. In addition, ghrelin is produced locally within the human and rodent gonads, where the presence of both components (ligand and receptor) of ghrelin signaling system is highly suggestive of a conserved regulatory role for this newly discovered molecule in the regulation of mammalian gonadal function. Overall, it is proposed that ghrelin may cooperate with other regulatory signals, such as leptin, in the integrated control of energy balance and reproduction.

Animals↗

Leptin exists in tubuli seminiferi and in seminal plasma.

Leptin is a 167-amino acid protein that stimulates gonadotrophin-releasing hormone secretion and exerts indirect effects on the gonads via neuropeptide Y, NPY. Recent research has suggested that leptin may also have an effect on testosterone secretion. To investigate the role of leptin in reproduction, leptin in testicular tissue and seminal plasma was examined in relation to leptin in serum, semen sample qualities and vasectomy. Seminal plasma and serum of 64 infertility patients, and 15 individuals after vasectomy, were assayed for leptin using a competitive 'in house' radioimmunoassay. The concentration of leptin in seminal plasma was significantly lower in the 'normal' semen sample group than in the 'pathological' group (Mean +/- SEM; 1.45 +/- 0.18 vs. 3.19 +/- 0.57 ng ml-1; P < 0.05), and showed a significantly negative correlation with percentage of motile spermatozoa (r = -0.46; P = 0.0005) and with the velocity straight line, VSL, (r = -0.30; P = 0.029). In contrast, leptin concentration in serum did not show any relationship with the spermiogram parameters. In testicular tissue, leptin was preferentially found within the tubuli seminiferi using anti-leptin polyclonal antibody, Ob A-20 Sc 842. The amount of leptin per ejaculate did not significantly change after vasectomy, and was not correlated to fructose, zinc or neutral alpha glucosidase in seminal plasma (P > 0.05). These results suggest that the amount of leptin in the genital tract, including the tubuli seminiferi, may influence the mechanisms involved in the motility development of spermatozoa.

Chromatography, Gel↗