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PubMedDate not supplied

Effect of intratesticular administration of anti-corticotropin-releasing factor antiserum (a-CRF) on testicular function in neonatal rats.

The possible physiological role of testicular corticotropin-releasing factor (CRF) in the regulation of testicular functions was studied in neonatal rats. Two microlitres of anti-CRF-antiserum (dilution: 1:10 or 1:100) was injected intratesticularly to 5 d-old rats with two testes and to hemicastrates. Five days after hemicastration and treatment of the remaining testis with the antiserum, serum testosterone concentration and basal testosterone secretion in vitro decreased significantly. Unilateral testicular injection of a-CRF in rats with two testes resulted in a significant drop in serum testosterone level with no change in basal testosterone production. Data indicate that in neonatal rats testicular CRF might be a local stimulator of steroidogenesis.

Animals↗
PubMed2002

Pharmacokinetics of a new transdermal testosterone gel in gonadotrophin-suppressed normal men.

OBJECTIVE: In a phase I single-centre, open, randomized study, the pharmacokinetics of two doses of a transdermal testosterone gel containing 2.5% testosterone were evaluated in 26 healthy male volunteers. DESIGN: To eliminate the influence of endogenous serum testosterone, gonadotrophins and endogenous testosterone secretion were suppressed by a single intramuscular injection of 400 mg norethisterone enanthate. Fourteen men applied 5.0 g and 12 men applied 2.5 g testosterone gel daily for 10 days. Half the men in each group washed the gel off 10 min after it had been applied. RESULTS: In all the men, a marked suppression of LH, FSH, testosterone, dihydrotestosterone (DHT) and oestradiol was observed after norethisterone treatment. Physiological serum concentrations of testosterone were restored during the 10-day treatment period in the group of men applying 5.0 g testosterone gel. Increasing serum concentrations of testosterone from day 1 to day 10 were observed. Oestradiol and DHT concentrations did not exceed normal values. Washing 10 min after gel application did not influence the resorption of testosterone. A dose of 2.5 g testosterone gel was insufficient to achieve physiological serum concentrations of testosterone. CONCLUSION: Testosterone replacement treatment with 5.0 g of this 2.5% testosterone gel is able to achieve constant physiological testosterone concentrations in gonadotrophin-suppressed men. Washing the skin after 10 min does not influence the pharmacokinetic profile and thus significantly reduces the risk of contamination of female partners or infants.

Adult↗
PubMed1993

Mixed gonadal dysgenesis: clinical, cytogenetic, endocrinological, and histopathological findings in 16 patients.

We describe clinical, cytogenetic, endocrine, and histopathological findings in 16 patients with mixed gonadal dysgenesis (MGD). All patients except 1 presented genital ambiguity and 10 of them had Ullrich-Turner manifestations. The 45,X/46,XY karyotype was the most frequent with a predominance of 45,X cells in both peripheral lymphocytes and gonads. In all cases Müllerian and Wolffian remnants and/or derivatives were found and in some patients both Wolffian- and Müllerian-derived structures were identified on the streak or testicular side. Postpubertal patients exhibited variable degrees of virilization and all of them had hypergonadotropism coexisting with low to normal baseline serum levels of testosterone; their testicular response to human chorionic gonadotropin (HCG) in terms of testosterone secretion was also variable, ranging from minimal to almost a normal response. All prepubertal patients but 1 had normal baseline levels of pituitary gonadotropins and testosterone and their gonadal response to the HCG challenge was highly variable. With the exception of 1 case, who had a 45,X/46,XY(p-) karyotype, no correlation between the cytogenetic data and degree of external genital ambiguity and the hormonal findings was observed. Additional information on the specific structural abnormalities involving the testis-determining gene of the Y chromosome in patients with MGD is needed in order to further understand the mechanisms responsible for the wide variability characteristic of this disorder.

Adult↗
PubMed1984

Absence of a direct inhibitory effect of the gonadotropin-releasing hormone (GnRH) agonist D-Ser (TBU)6, des-Gly-NH2(10) GnRH ethylamide (Buserelin) on testicular steroidogenesis in men.

The antigonadal effects of GnRH agonists (GnRH-A) are mediated both through pituitary and testicular inhibitory mechanisms in the rat. To investigate these effects in men, we studied patients having no gonadotropin secretion and compared their testicular response to hCG in the absence or in the presence of GnRH-A. Thirteen patients with acquired pituitary hypogonadotropism had plasma testosterone levels below 1.5 ng/ml and no gonadotropin responses to acute GnRH administration (100 micrograms iv). Testicular responsiveness was evaluated using a single im injection of hCG (5000 IU im). Plasma levels of testosterone, dihydrotestosterone, androstenedione, 17-hydroxyprogesterone (17-OHP), and progesterone were determined before and 4, 12, 24, 48, and 72 h after hCG stimulation. The same protocol was also used in the same patients on day 4 of a 6-day course of treatment with the GnRH-A, D-Ser-(TBU)6, des-Gly NH2 GnRH ethylamide (Buserelin) (3 sc injections of 250 micrograms/day). During the first 4 days of GnRH-A administration, plasma LH, FSH, and testosterone levels were measured daily in order to establish the completeness of the gonadotropin deficiency. Before treatment with hCG, plasma testosterone levels were 0.56 +/- 0.15 and 0.96 +/- 0.22 ng/ml (mean +/- SE) in the absence of GnRH-A and during GnRH-A administration, respectively. The administration of hCG elicited a significant increase in plasma testosterone in both situations; integrated testosterone concentrations were 123.7 +/- 24.9 and 155.5 +/- 27.9 ng/ml . 72 h (P greater than 0.1) in the absence of GnRH-A and during GnRH-A administration, respectively. Likewise the ratios of 17-OHP to progesterone, androstenedione to 17-OHP, and dihydrotestosterone to testosterone after hCG injection were similar in the presence or absence of GnRH-A. Since short term administration of buserelin did not inhibit hCG-induced testosterone secretion in patients with gonadotropin deficiency, we suggest that Buserelin does not grossly modify the function of testicular steroidogenesis enzymes. The antigonadal effects of GnRH-A in man appear to be mediated exclusively through the pituitary.

Buserelin↗
PubMed1981

Testosterone concentrations in spermatic venous blood plasma of prepubertal boys.

Testosterone concentration has been measured in spermatic and peripheral venous plasma obtained during surgery from a total of 25 prepubertal boys affected either by inguinal hernia (Group I; N = 6; age range 2-8 years) or unilateral undescended testis (Group II; N = 19; age range 5-11 years). Median spermatic venous testosterone level was 58.7 ng/dl) (range 14.0--120.8 ng/dl) in Group I and 43.2 ng/dl (range 12..2-267.5 ng/dl) in Group II; median peripheral testosterone level was 4.9 ng/dl (range 2.3-15.4 ng/dl) and 5.6 ng/dl (range 1.1-89.3 ng/dl) in Group I and II, respectively. The difference between the spermatic and peripheral level was statistically significant in both groups (P less than 0.01 in Group I and P less than 0.001 in Group II). These results indicate that the prepubertal human testis secretes testosterone, even if in a very low amount. It is also suggested that this secretion can be responsible for LH inhibition in prepubertal boys.

Child↗
PubMed1989

Ontogeny of pulsatile gonadotrophin secretion and pituitary responsiveness in male puberty in man: a mixed longitudinal and cross-sectional study.

The onset of puberty is characterized by a sleep-associated increase in pulsatile LH secretion which is not observed in adults. The ontogeny of gonadotrophin secretion during pubertal maturation may reflect changes in endogenous LHRH secretion, pituitary sensitivity to LHRH and/or alterations in gonadal steroid feedback. To understand the interplay between these mechanisms, we have examined the pulsatile pattern of plasma LH, FSH, testosterone, oestradiol and prolactin between 20.00 and 09.00 h and the pituitary response to repeated exogenous LHRH stimulation in 16 boys with delayed puberty (age 16.3 +/- 2.7 (S.E.M.) years) on one to four occasions in a mixed longitudinal/cross-sectional analysis. Physical maturity was determined by Tanner G staging (1-5) and clinical progress followed for a mean duration of 22.4 +/- 8.5 months during which 33 hormone profiles were obtained. Nocturnal (23.00-09.00 h) LH pulse frequency increased to a peak of 0.54 +/- 0.03/h at stage 2 which was followed by a gradual decline to 0.42 +/- 0.04/h at stage 5. The appearance of LH pulses in the evening (20.00-23.00 h), probably representative of the rest of the day, was delayed until mid-puberty from which point frequency increased to a peak of 0.53 +/- 0.08/h at stage 5. LH pulse amplitude showed a linear increase from stages 1 to 5, with nocturnal pulse amplitudes being higher than evening pulses throughout. FSH did not show a clear pulsatile pattern. The LH:FSH ratio reversed from less than 1 to greater than 1 at stage 2. The LH response to exogenous LHRH increased in parallel with LH pulse amplitude. There was no difference in the pattern of LH response to repeated LHRH stimulation as puberty advanced; the first stimulus always elicited a greater response than subsequent doses. In contrast, the FSH response to LHRH was maximal at stage 1 and became attenuated thereafter. The estimated mean nocturnal LHRH concentration or amplitude did not show any increase during pubertal maturation from 20.42 +/- 11.57 at stage 1 to 35.96 +/- 20.83 ng/l at stage 5. In conclusion, the sequential changes in this study suggest that the sleep-entrained increase in LHRH pulse frequency plays a key role at the onset of puberty. By enhancing pituitary responsiveness and setting in motion a cascade of events, this peripubertal augmentation of LHRH pulse frequency can account for most of the subsequent changes in LH, FSH and testosterone secretion during pubertal development in the male without any apparent alteration in LHRH pulse amplitude.

Adolescent↗
PubMedDate not supplied

Elevated daytime urinary excretion of testosterone glucuronide in men with the type A behavior pattern.

Urinary excretion of testosterone glucuronide was compared in 13 men with typical Type A behavior pattern (as determined by structured interviews) and 10 age-matched men with typical Type B behavior pattern. Twenty-four hour urine collections were divided into three periods: 9AM - 6PM , 6PM to bedtime, and bedtime to 9AM . Type A men showed a significantly higher excretion than Type B men in the daytime ( 9AM - 6PM ); the geometric mean value was 24 micrograms in Type A and 15 micrograms in Type B (P less than 0.05). There were no significant differences between Type A and Type B men for the other two time periods. Indicating an elevated daytime testosterone secretion in Type A men, this finding is consistent with a recent report that exposure to laboratory tests of reaction time causes an increase in plasma testosterone levels in Type A but not Type B men. Since a role for testosterone in the genesis of coronary heart disease (CHD) is suggested by the much higher incidence of CHD in men and the acceleration of murine atherogenesis by testosterone, the findings of this and the previous report may represent a mechanism for the elevated incidence of CHD in Type A men.

Adult↗
PubMed1992

Sex difference in the effect of mating on c-fos expression in luteinizing hormone-releasing hormone neurons of the ferret forebrain.

The pulsatile secretion of LH was previously found to rise in female ferrets after receipt of an intromission, whereas in males that achieved an intromission, both LH and testosterone secretion were either reduced or unchanged. We sought to determine whether this sexually dimorphic pattern of LH secretion reflects a sex difference in the effect of mating on the activity of forebrain neurons that secrete LHRH. Immunocytochemical methods were used to localize the nuclear protein product of the immediate early gene, c-fos, as an index of increased neuronal activity after mating. Nuclear FOS immunoreactivity (FOS-IR) was monitored in LHRH-IR neurons as well as other non-LHRH forebrain neurons. In confirmation of previous reports, LHRH-IR perikarya in ferrets of both sexes were located medially along the base of the brain at rostral, medial, and caudal levels of the preoptic-hypothalamic continuum. In each of these regions a significantly higher percentage of LHRH-IR neurons was colabeled with nuclear FOS-IR in mated than in unpaired females. By contrast, an equivalent low percentage of LHRH-IR neurons was colabeled with FOS-IR in mated and unpaired male ferrets. Significantly more FOS-IR neurons (not colabeled with LHRH) were detected in the bed nucleus of the stria terminalis, the medial preoptic area, the dorsal-medial hypothalamus, and the medial amygdala (MA) of mated vs. unpaired females. By contrast, mating significantly augmented FOS-IR only in the MA of male ferrets. The results suggest that the sexually dimorphic pattern of LH secretion that occurs in ferrets after mating reflects a selective activation of LHRH neurons in the female forebrain. This sex-specific increase in the responsiveness of LHRH neurons to mating may depend on input from a limbic circuit which includes the medial amygdala, bed nucleus of the stria terminalis, and medial preoptic area.

Animals↗
PubMed2002

Localization of the cytochrome p450 side-chain cleavage enzyme in the inactive testis of the naked mole-rat.

Spermatogenesis was histologically examined in non-breeding male of the naked mole rat (Heterocephalus glaber) using a light microscopy. Spermatogonia, spermatocytes and spermatids were confirmed in the seminiferous tubules. However, the spermatogenesis was disordered, and many spermatocytes and spermatids were sloughing. Sperms could not be seen in the lumen of the tubules. The characteristic accumulation of interstitial cells was the most noteworthy. In the immunohistochemistry for cytochrome p450 side-chain cleavage enzyme, immunoreactions were not entirely distributed in each interstitial cell, although positive reactions were scattered in the interstitial cell-mass. The findings indicate that few interstitial cells act as a testosterone-synthesizing apparatus in the characteristic structure with accumulated cell-mass. From the immunohistochemical data we suggest the possibility that spermatogonia and Sertoli cells may secrete 17 beta-estradiol. We also suggest that 17 beta-estradiol from spermatogonia and Sertoli cells may inhibit the interstitial cells from synthesizing and secreting testosterone and may suppress the later stages of the spermatogenesis to induce apoptosis of germ cells. The TUNEL methods demonstrated that cell death occurred in some spermatocytes in non-breeding males.

Animals↗
PubMed2004

The effects of pharmacologically induced hypogonadism on mood in healthy men.

BACKGROUND: The effects of declining androgen secretion on mood regulation and the potential psychotropic efficacy of androgen replacement in men are largely undetermined. OBJECTIVE: To examine the effects on mood of the acute suppression of testosterone secretion. DESIGN: A double-blind, placebo-controlled, crossover (self-as-own-control) study. SETTING: An ambulatory care clinic in a research hospital. PARTICIPANTS: Thirty-one healthy adult men with no history of psychiatric illness or substance or anabolic steroid abuse. INTERVENTIONS: Men received depot leuprolide acetate (Lupron, 7.5 mg intramuscularly) every 4 weeks for 3 months. After the first month of Lupron alone, all men received (in addition to Lupron) testosterone enanthate (200 mg intramuscular) or placebo (sesame oil as color-matched vehicle) every 2 weeks for 1 month each in a crossover design. The order of administration of testosterone and placebo was randomly assigned and counterbalanced. MAIN OUTCOME MEASURES: Mood and behavior rating scores (self-report and rater administered). RESULTS: With the exceptions of hot flushes, libido, and the feeling of being emotionally charged, none of the symptoms measured showed a significant difference across eugonadal, Lupron plus placebo, and Lupron plus testosterone conditions. Despite the absence of a uniform effect of Lupron plus placebo on mood, 3 men experienced clinically relevant mood symptoms during this induced hypogonadal condition. High baseline levels of sexual functioning predicted the greatest decline in sexual function during Lupron plus placebo. CONCLUSIONS: These data, the first to describe the effects on mood of induced hypogonadism in healthy young men, suggest that short-term hypogonadism is sufficient to precipitate depressive symptoms in only a small minority of younger men. The predictors of this susceptibility remain to be determined.

Adult↗
PubMed1976

[Effect of neonatal injections of estradiol, testosterone and cryproterone acetate on plasma and testicular testosterone and on the genital system in adult male mice].

On day old male mice received a single injection of oestradiol benzoate, testosterone propionate or cyproterone acetate in order to study their action on testicular development, particularly testosterone secretion. Oestrogenization of newborn males leads, when the animals mature, to a high proportion or cryptorchidism, to atrophy of testes and seminal vesicles, and inhibition of spermatogenesis. Testosterone levels were reduced in the plasma. Testosterone propionate produced moderate reduction of testicular weight but spermatogenesis was not impaired. Plasma testosterone level was reduced. Cyproterone acetate increased significantly testicular testosterone level.

Animals↗
PubMed1979

Testosterone metabolism in normal males and male cirrhotics.

The following physiopathological mechanisms for the abnormalities of testosterone metabolism observed in cirrhotic patients may be postulated: 1. The decreased testosterone secretion has a primary testicular origin; it seems probable that, as a result of direct toxicity the 17-beta-reductase is inhibited, resulting in decrease of testosterone and an increase of androstenedione. 2. The hypothalamic-pituitary function is nearly normal in cirrhotics. Basal level of LH and FSH are often slightly elevated, indicating a normal reactivity of the pituitary. 3. The conversion of androgens to oestrogens (androstenedione to oestrone) which occurs essentially extrahepatically, is increaed in cirrhosis.

Adipose Tissue↗
PubMed1977

Testosterone synthesis in vitro by the fetal testis of the guinea pig.

Synthesis and secretion of testosterone by testes of guinea pig fetuses were studied in organ culture. The amount of testosterone secreted into the culture medium was estimated by radio-immunoassay. It was demonstrated that testosterone was already secreted by testes explanted at 25 days. The amount of testosterone secreted during the first day in culture by testes from fetuses of different ages (25-30 days) increased with fetal age. The amount of testosterone extracted from fetal guinea pig testes at ages used for explantation (25-30 days) were much lower than the amount secreted during the first 24 hours in culture. During subsequent days in culture, an increase in the amount of testosterone secreted was observed only for testes explanted at 25 days. The amount secreted by testes from older fetuses (26-30 days) stayed constant or decreased. Aminogluthetimide phosphate (100 micron) decreased significantly testosterone secretion by testes explanted at 25 days. These findings indicate that the capacity for biosynthesis of testosterone is present in fetal guinea pig testes at 25 days and increases during the subsequent days.

Aminoglutethimide↗
PubMed1993

Age-related decline in the steroidogenic capacity of isolated rat Leydig cells: a defect in cholesterol mobilization and processing.

This study was designed to evaluate the effects of aging on steroidogenesis and intracellular cholesterol processing in rat Leydig cells. Maximum gonadotropin-induced testosterone secretion was significantly reduced in Leydig cells from 18 to 27-month-old rats compared to 2 to 5-month-old rats. The decreased production of testosterone in older groups persisted after incubation with cAMP analogs or other non-specific stimulatory agents. This age-related loss in testosterone response was not due to changes in gonadotropin receptor concentration, cAMP concentration, protein kinase A activation or the activity of key steroidogenic enzymes. The content of cellular cholesteryl esters doubled as rats aged from 5 to 18 months, and this high cholesteryl esters level remained constant through 27 months. The ability of hCG to mobilize (hydrolyze) stored cholesteryl ester for testosterone production was significantly reduced (65-75%) in cells from the older rats. This change could be accounted for by the decline in activity of neutral cholesteryl esterase in Leydig cells from 18-month-old rats. In contrast, the activity of a non-specific lysosomal acidic cholesteryl esterase did not change with age. The activity of HMG CoA reductase, the rate limiting enzyme in cholesterol biosynthesis decreased about 70% between 5 and 18 months and fell slightly further as the rats aged to 27 months. Also, [14C]acetate or [3H]H2O incorporation into cellular sterols showed a similar decline. Cyanoketone plus hCG stimulated pregnenolone production was reduced about 70-80% in old as compared to young cells. Leydig cells from young rats responded to hCG with increased accumulation of mitochondrial cholesterol in the presence and absence of steroidogenic inhibitors. On the other hand, old cells responded poorly to hCG and mitochondrial cholesterol levels were little affected by hCG plus cycloheximide or aminoglutethimide. Together, these data indicate that alterations in the intracellular processing and metabolism of cholesteryl esters occur in Leydig cells of aging rats, and we suggest they may be responsible for the observed age-related changes in testosterone production.

Aging↗
PubMed1982

Plasma testosterone during bicycle ergometer exercise without and after L-dopa pretreatment.

The level of testosterone in plasma during submaximal, prolonged submaximal and maximal exercise on a bicycle ergometer was measured in healthy untrained men. To evaluate the possible involvement of prolactin in the regulation of testosterone secretion during exercise, the influence of prolactin inhibition by oral L-dopa (1 g) pretreatment was also studied. The exercise evoked a small but significant rise of testosterone concentration with peak levels immediately at the end of work performance or 10 min after that. No substantial difference between the response to submaximal and maximal exercise was noted. In these experiments the findings by others on a lack of plasma LH changes and significant increase of plasma prolactin were confirmed. Pharmacological blockade of prolactin release by L-dopa pretreatment failed to modify the response of testosterone to bicycle ergometer exercise. It may be suggested that prolactin is not involved in the induction of plasma testosterone increase during physical exercise.

Adult↗
PubMed2002

Vernal changes in the behavioral and endocrine responses to GnRH application in male European ground squirrels.

This field study was aimed at examining hypothalamic involvement in the behavioral changes of male European ground squirrels (Spermophilus citellus) before, during, and after the mating season. The effects of exogenous gonadotropin-releasing hormone (GnRH) application on androgen secretion and behavioral patterns were investigated. Animals were captured, bled, and injected intramuscularly with 40 ng/100 g of GnRH. A second plasma sample was collected 40 min after the treatment to document changes in testosterone secretion. Behavioral parameters such as intra-sexual aggression, scent marking, and home range size were compared on the days before and after the stimulation. In the first two phases, before female emergence and during mating, GnRH-injection caused increases in plasma testosterone. In the post-mating phase, initial plasma testosterone levels had decreased and no elevation could be induced. Sham treatment of controls had no effect in any phase. Conditional parameters like emergence body mass and testicular size covaried with androgen increases only in the pre-mating period. Behavioral changes after GnRH administration occurred during the pre-mating period. Intra-sexual aggression, scent marking, and home range size increased significantly in experimental individuals. Later, during mating and post-mating, we found no behavioral changes associated with the GnRH treatment or the testosterone increase. The results demonstrate changes in the endocrine and behavioral sensitivity to GnRH application, according to the phases of the active season. An exogenous pulse of GnRH can apparently release behavior in male European ground squirrels, which is normally context dependent with the emergence of females.

Aggression↗
PubMed1975

Changes in plasma levels of LH, FSH and testosterone following the administration of synthetic luteinizing hormone-releasing hormone to cryptorchid patients.

The levels of LH, FSH and testosterone of three adult groups consisting of normal subjects, unilateral and bilateral cryptorcids were compared before and after LH-RH loading. It was found that both groups of cryptorchid had comparatively high plasma base line levels for both LH and FSH, particularly high in the bilateral group; and both groups responded to LH-RH loading. This indicates that their hypothalamo-hypophyseal systems were probably functioning normally. The plasma base line levels of testosterone were higher in unilateral cryptorchids than in the control group, and lowest in the bilateral cryptorchid group. But the reaction of testosterone levels to LH-RH loading was generally poor in both groups of cryptorchids, suggesting that, in cryptorchid cases, unilateral and bilateral, the capacity of the testicle to secrete testosterone is generally depressed, freeing central suppression. This probably accounts for the high values of plasma lh and FSH observed in such patients.

Adolescent↗
PubMed1993

Hormonal responses to the new potent GnRH antagonist Cetrorelix.

GnRH antagonists, unlike the GnRH agonists, immediately suppress gonadotropins and testosterone secretion without initial stimulatory effect. We report here on a single-dose study with the new GnRH antagonist Cetrorelix (Ac-D-Nal(2)1, D-Phe(4C1)2, D-Pal3, D-Cit6, D-Alal0) in 25 normal men. The study involved five different dose groups (0.25, 0.5, 1.0, 1.5 or 3.0 mg) and subjects were observed over a 40 h period. Five men served as controls. Serum levels of LH, FSH and testosterone decreased rapidly with a dose-related decline for testosterone of 25%, 24%, 41%, 53% and 72%, respectively, for testosterone within the first 8 h of antagonist administration. All effects were reversible and no serious side effects were observed. Thus, this GnRH antagonist is active in men even in small doses and could become a new therapeutic tool for sex hormone-dependent diseases. Cetrorelix seems to have the highest suppressive rate per mg peptide of all other antagonists from the literature, such as Nal-Glu (Ac-D-Nal(2)1, D-Phe(4Cl)2, D-Pal3, Arg5, D-Glu6(AA), D-Alal0), Detirelix (Ac-D-Nal(2)1, D-pCl-Phe2, D-Trp3, D-hArg(Et2)6, D-Alal0) or 4F (Ac-delta 3Prol, 4F-D-Phe2, D-Trp3,6). During the time of suppression after a dose of 3 mg there was an LH and testosterone peak in the early morning coinciding with the testosterone peak in untreated men. The GnRH antagonist seems to unmask the circadian rhythm of LH secretion.

Adult↗