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Testosterone implants into the lateral septum of male rats, a positive effect on LH and FSH secretion.

After two days, testosterone implanted into the lateral septum increased serum levels of LH and FSH in male Wistar rats. As measured by RIA, LH in animals with testosterone implanted in them in comparison to those with an empty cannula was 0.220 +/- 0.015 vs. 0.111 +/- 0.019 ng/ml; p less than 0.001 and FSH was 3.20 + 0.21 vs. 1.50 + 0.21 ng/ml; p less than 0.001. Serum testosterone was not increased to a statistically significant extent by the implants (4.12 +/- 0.54 vs. 2.87 +/- 0.42 ng/ml; ns). It was concluded that testosterone or possibly one of its metabolites acting in the lateral septum facilitates the release of LH and FSH.

Animals↗

A longitudinal study of leptin during development in the male rhesus monkey: the effect of body composition and season on circulating leptin levels.

The objective of this study was to examine longitudinal changes in serum leptin concentrations during development and to correlate those changes with sexual development in male rhesus monkeys housed under natural environmental conditions. Blood samples were drawn from 8 control animals approximately every other month from 10 to 30 mo of age and thereafter monthly through 80 mo of age. Leptin levels declined through the juvenile period until the onset of puberty and were negatively correlated with body weight. Seven of the eight animals became sexually mature during the breeding season of their fourth year of life. Puberty was delayed in the other animal until the subsequent breeding season. There were no significant fluctuations in leptin levels prior to or in association with the pubertal rise in LH and testosterone (T) secretion. During the peripubertal period, levels of leptin varied between 2 and 3 ng/ml. The animal that exhibited delayed puberty had the lowest body weight and highest leptin levels during this period. With the achievement of sexual maturity, leptin levels varied seasonally, with peak levels in the late winter (Jan-Mar) and a nadir in the late summer (Aug-Sept). A late winter rise in leptin was also evident in most of the animals during Years 2 and 3, but not during Year 4. In the fall of Years 5 and 6, the seasonal rise in leptin concentrations lagged 3-4 mo behind the seasonal increase in LH and T. In the fall of Year 5, but not thereafter, leptin levels were positively related to percent body fat and negatively correlated with lean body mass. The data do not support the hypothesis that increasing leptin concentrations trigger the onset of puberty in the male rhesus monkey. During the juvenile period and after sexual maturation, but not during the peripubertal period, leptin secretion varied with season in the animals; but the environmental factors that cue or drive this rhythm remain to be determined.

Aging↗

Ageing of the neuroendocrine system in the brain of male rats: receptor mechanisms and steroid metabolism.

The work described in this article gives information on the effects of ageing on the hypothalamo-pituitary-testicular axis in rats. The hypothalami of young and old male rats contain similar amounts of luteinizing-hormone-releasing hormone (LHRH); when perifused in vitro they release comparable amounts of LHRH under basal conditions and in response to K+. The addition of an LHRH analogue to the perifusion medium blocks the release of LHRH induced by K+ from the hypothalami of young and old male rats, indicating that the ultrashort feedback mechanism controlling LHRH release functions normally in aged male rats. Ageing also exerts important effects on the density of mu- and kappa-opioid receptors in the brain. The number of hypothalamic mu-opioid receptors was significantly decreased in aged animals; a replacement treatment with testosterone does not reverse this decrease, indicating that the decline of hypothalamic mu receptors and of serum titres of testosterone in old rats are independent phenomena. The number of kappa-opioid receptors in the brain increases in the amygdala and in the thalamus with ageing. Apparently ageing does not influence the number of delta receptors in any of the brain areas investigated. The number of pituitary LHRH receptors decreases in old animals, which might explain the low serum concentration of gonadotrophins in aged rats caused by an inadequate response of the pituitary to hypothalamic LHRH. The impaired secretion of testosterone in aged male rats is accompanied by an increase in the number of testicular LHRH receptors, indicating that the intratesticular mechanisms controlling testosterone release also undergo significant alterations during ageing. The rate of conversion of testosterone to dihydrotestosterone (DHT) and 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha-diol) is the same in the hypothalami of young and old rats. However, the yields of DHT obtained from the pituitaries of aged male rats are significantly lower than those recorded in the pituitaries of young animals. These results show that the enzymes necessary for metabolizing testosterone via the 5 alpha-reductase pathway are maintained both in the hypothalamus and in the anterior pituitary of aged male rats. However, the 5 alpha-reductase activity of the anterior pituitary of senescent animals appears to be lower than that in the younger controls.

Aging↗

Effects of nutrition on testicular size and the concentrations of gonadotrophins, testosterone and inhibin in plasma of mature male sheep.

The effects of nutrition on the hypothalamo-pituitary-gonadal axis were studied in three groups of six mature Merino rams that were fed for 56 days with a ration that maintained their initial live mass (intermediate diet: 675 g chaff plus 175 g lupins), the same ration with a lupin supplement (high diet: 675 g chaff plus 825 g lupins), or about half of the intermediate ration (low diet: 475 g chaff plus 125 g lupins). Lupin seed provides a highly (95%) digestible source of energy and protein. Plasma concentrations of LH, FSH, testosterone and inhibin were measured in blood samples collected over 24 h on the day before dietary treatments began (day-1), then on days 0, 1, 5, 14, 28 and 56. Compared with the intermediate diet, the high diet significantly increased live mass within 14 days and testicular size within 28 days, and these differences increased steadily throughout the experiment. Plasma FSH concentrations and LH pulse frequency increased within 5 days, but these effects were maintained for only 14 days. Decreasing the nutritional status reduced live mass and testicular size within 7 days, led to a low LH pulse frequency that persisted throughout the experiment, but did not affect FSH concentrations. Significantly less testosterone was secreted over 24 h in the low dietary group than in the intermediate or high group until day 28. The high group tended to secrete more than the intermediate group, but only at the beginning of the experiment when LH pulse frequencies differed between these groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Nutritional Physiological Phenomena↗

Fetal development of Leydig cell activity in the mouse is independent of pituitary gonadotroph function.

During fetal development the testes secrete anti-Mullerian hormone and testosterone to induce formation of the male phenotype. Adult Leydig cells secrete testosterone under the control of LH, but the role of the fetal pituitary in regulating fetal Leydig cell function is unclear. To study the early relationship between pituitary and Leydig cell function, we have examined the development of fetal pituitary LH levels and Leydig cell function in normal mice and in hypogonadal (hpg) mice that lack GnRH and, thus, circulating gonadotropins. In normal and hpg mice, pituitary LH content was barely detectable until embryonic day 17 (E17), when levels began to increase significantly in both groups. Pituitary levels of LH in hpg mice were, however, only about 10% of normal at all ages. Full-length LH receptor transcripts were first detectable in fetal testes on E16 in both normal and hpg mice. In normal mice, levels of testicular messenger RNA (mRNA) encoding cytochrome P450 side-chain cleavage and 17alpha-hydroxylase increased from E13 to reach a peak around birth. In hpg mice, levels of mRNA encoding these enzymes were normal until around birth, at which time there was a significant decline. Levels of testicular mRNA encoding 3beta-hydroxysteroid dehydrogenase type I were similar in normal and hpg mice and showed little change during development. Intratesticular testosterone reached a peak on E18 in normal animals before declining again after birth. In hpg mice, intratesticular testosterone levels were normal throughout fetal development and on the day of birth, but were barely detectable by postnatal day 5. Results show 1) that fetal Leydig cell function in the mouse is normal in the absence of endogenous circulating gonadotropins; 2) that Leydig cells become dependent on gonadotropins shortly after birth; and 3) that pituitary LH synthesis can start in the absence of GnRH but is dependent on LH for a normal level of synthesis and secretion.

Animals↗

Influence of mesonephros on foetal and neonatal rabbit gonads. I. Sex-steroid release by the testis in vitro.

The experiments were performed to study the influence of mesonephros on gonadal sex hormone release. Foetal and neonatal rabbit testes were cultured for 5 days, with and without their mesonephric tissue. The culture media were harvested every day and analyzed by RIA for the content of testosterone, progesterone and oestradiol. The development of the tissues were evaluated microscopically after culturing. The results show that between day 20 pc and day 1 pp the mesonephric tissue lowered the amounts of testosterone in co-cultures with testis. This effect disappears when the mesonephric derived cells develop the capacity to synthesize a meiosis inducing substance (MIS). A relationship between decrease of testosterone and secretion of MIS is discussed. It is concluded that the steroid producing cells of the testis, the Leydig cells, originate or are heavily influenced by mesonephros during early testicular organogenesis.

Animals↗

Saliva testosterone time-course response to hCG in adult normal men. Comparison with plasma levels.

Testosterone time-course response to 5000 IU hCG was studied simultaneously in the saliva and the plasma of 13 adult normal men. Baseline levels in saliva and plasma were: 93 +/- 9 pg/ml (mean +/- SEM) and 4.9 +/- 0.3 ng/ml respectively. After hCG the same biphasic pattern was observed in both fluids with a similar early response but the delayed peak at 72 h was relatively higher in saliva than in plasma. Thus it was suggested to collect saliva instead of plasma for the evaluation of testicular secretion of testosterone after hCG administration.

Adult↗

Developmental changes in testicular gonadotropin receptors: plasma gonadotropins and plasma testosterone in the rat.

The relationships between plasma gonadotropins, testicular gonadotropin receptors, and plasma testosterone were examined during neonatal life and throughout sexual maturation in the rat. The binding affinity of testicular LH receptors (2.4 X 10(10) M-1) was significantly higher than that of FSH receptors (2.1 X 10(9) M-1) at all stages of development. The concentration of FSH receptors in the testis reached a peak between 10-15 days of age, then fell to a constant level from 25-90 days. However, the testis content of FSH receptors increased continually with age and reached a plateau at day 60. Plasma FSH declined after birth to a nadir at 15 days, then rose rapidly to a peak at day 38, and fell to a plateau from day 50 through adult life. In contrast to the rapidly changing profile of plasma FSH during early maturation, alterations in plasma LH were less marked throughout development. Although a progressive rise in plasma LH concentration was observed between days 36-51, the simultaneous changes in testicular LH receptors and plasma testosterone were much more prominent. Testicular LH receptors showed a continuous increase in concentration and total number with advancing age and testis growth. The major rise in LH receptor concentration occurred between 15-38 days age, at the same time as the rise in plasma FSH concentration and the phase of rapid testicular growth. Plasma testosterone fell during the 8th-24th days after birth, then rose rapidly between days 35-55. The pubertal rise in plasma testosterone occurred about 15 days after testicular LH receptors began to increase and was coincident with the continuing rise in LH receptor content from day 35 until day 55 and with the progressive increase in plasma LH during this period. These observations have demonstrated that the early development of testicular FSH receptors in followed by a prominent rise in plasma FSH, with concomitant increases in testicular growth and LH receptor concentration. The resulting increase in gonadal sensitivity to LH could be responsible for the marked increase in secretion of testosterone which occurs during puberty in the presence of a relatively small change in the circulating LH concentration. The sequence of changes observed in gonadotropins and their testicular receptors is consistent with the view that FSH-induced testicular sensitivity to LH is an important factor in sexual maturation in the male rat.

Aging↗

Hypergravity does not affect testicular function.

BACKGROUND: A previous study revealed that exposure of rats to microgravity for 14 d on Cosmos 2044 reduced production of testosterone by > 80%, although spermatogenesis remained essentially normal. METHODS: To ascertain if testicular function was altered in hypergravity, 60-d-old rats were randomly assigned to 2 groups (10 per group) and subjected to 14 d of centrifugation to expose them to a total of 2G, or held at unit gravity in similar cages without centrifugation (control). RESULTS: After 14 d, body weight of 2G rats was essentially unchanged, whereas that of control rats had increased; 310 vs. 377 g (p < 0.05). Testes weight, production and secretion of testosterone, diameters of seminiferous tubules and their lumina, data from subjective evaluation of spermatogenesis, and counts of homogenization-resistant spermatids all were similar for 2G and control rats. CONCLUSION: It was concluded that exposure of male rats to 2G for 14 d had no major effect on testicular function whereas, based on earlier studies, exposure to microgravity (< 10(-3) x gravity) for 11-14 d suppressed production of testosterone by Leydig cells and reduced concentrations of anabolic steroids available to peripheral tissues.

Animals↗

The effects of one- and two-stage orchiopexy on postoperative serum testosterone levels and testicular volume in adult patients with bilateral nonpalpable testes.

In this study, we investigated the effects of one- and two-staged orchiopexy on testicular volume and serum testosterone levels in cases with high, abdominally localized, bilateral nonpalpable testes. Between March 1996 and April 2001, orchiopexy was performed on 46 testes in 23 patients with bilateral nonpalpable testes. In 15 of the 23 patients, a two-stage Fowler-Stephens orchiopexy was performed, and in 8 of the 23 patients, a one-stage laparoscopic orchiopexy was performed. For one patient who lacked both testes, bilateral prosthetic testes were inserted. The patients' ages were between 20 and 23 years (average, 21 years). In the first stage of the two-stage orchiopexy, the spermatic artery was ligated laparoscopically. Six months later, open surgery orchiopexy was performed. Patients were followed for 2 to 16 months (average, 10 months) and were evaluated for testicular atrophy, serum testosterone levels, and complications. In all the patients, the preoperative secondary sexual characteristics and serum testosterone levels were normal. Among the postoperative controls, evaluated at months 3 and 6, one patient's testes were found at the pubic area. Testicular atrophy was not observed in any of the patients, and the serum testosterone levels were in the normal range. In the two-stage orchiopexy group, 5 (33%) of the 15 patients had an average 30% volume decrease, and in the one-stage group, 2 (25%) of the 8 patients had an average 40% volume decrease. In this study, it was shown that either two-stage Fowler-Stephens orchiopexy or laparoscopic orchiopexy can be successfully performed in patients with bilateral abdominal testes, and that the testes can be fixed to their palpable original positions without interfering with the secretion of testosterone. Although the results are similar, our experience suggests that single-stage laparoscopic orchiopexy is the preferable method.

Adult↗

Production of recombinant orange-spotted grouper (Epinephelus coioides) luteinizing hormone in insect cells by the baculovirus expression system and its biological effect.

The cDNA sequence encoding orange-spotted grouper lhb (LHbeta) and cga (GTHalpha) subunits were cocloned into baculovirus transfer vectors and expressed in insect Sf9 cells. The results showed that two bands of 15.6 kDa and 11.4 kDa could be detected by SDS-PAGE and a band of 30 kDa could be detected by native PAGE. The recombinant grouper Lh (rgLh) could stimulate the secretion of testosterone (T) and estradiol-17beta (E2) from the gonad in a static incubation system in a time-dependent, but not a dose-dependent, manner. Using in vivo bioassay, the mRNA levels of two aromatases (cyp19a1a [P450aromA] and cyp19a1b [P450aromB]), gnrh (GnRH), lhb, and cga in the pituitary, gonad, and hypothalamus were determined in different groups of orange-spotted groupers treated respectively with rgLh, human chorionic gonadotropin (hCG), and a culture medium of insect cells transformed with an expression vector without lhb and cga subunits. The mRNA levels of cyp19a1a and cyp19a1b rose dramatically after injecting rgLh intraperitoneally, which was consistent with the secretion of sex steroid hormones. Interestingly, the mRNA levels of gnrh dropped in the pituitary, hypothalamus, and gonad, and the mRNA levels of lhb and cga in the pituitary of the experimental group expressed at a higher level than that of the hCG group. These results are in accord with the long positive feedback loop of Lh on gonad sex steroid hormones and the short negative feedback loop of Lh on gnrh mRNA levels. These results indicate that the rgLh is successfully expressed by the baculovirus-insect expression system and that the rgLh has biological activity.

Animals↗

Effects of psychoactive and nonpsychoactive cannabinoids on the hypothalamic-pituitary axis of the adult male rat.

The acute dose-response effects of delta-9-tetrahydrocannabinol (THC), cannabinol (CBN) and cannabidiol (CBD) on gonadotropin and testosterone (T) secretion and on hypothalamic norepinephrine (NE) metabolism were tested in adult male rats. THC and CBN both produced an acute suppression of plasma-luteinizing hormone (LH) and T levels and median eminence NE turnover although a dose-response relationship could not be demonstrated. CBD had no significant effect on any of these parameters and none of these cannabinoids had any effect on plasma follicle-stimulating hormone levels or median eminence LH-releasing hormone (LHRH) content. Except for the highest dose of CBN, none of the in vivo cannabinoid treatments significantly altered in vitro LH secretion although there was a trend towards decreased LH secretion. These results suggest that the decrease in LH secretion in THC- or CBN-treated rats is due to reductions in NE stimulation of LHRH release rather than to changes in LHRH synthesis or pituitary LHRH response.

Animals↗

Arachidonic acid is involved in the regulation of hCG induced steroidogenesis in rat Leydig cells.

Phospholipase C (PLC), an enzyme involved in the hydrolysis of membrane phospholipid- phosphatidylinositol-bisphosphate to inositol triphosphate and diacylglycerol, and Phorbol 12, myristate 13, acetate (PMA), a tumor promoting agent, could significantly stimulate testosterone (T) secretion from Leydig cells. Arachidonic acid (AA) stimulated T secretion by about 2 fold. The steroidogenic effect of PLC and AA was biphasic. At low concentrations both PLC and AA (100 mU and 12.5 microM, respectively) augmented hCG induced T secretion, while at higher concentrations (PLC: 500 mU and AA: 200 microM) they inhibited steroid production. AA also had a biphasic effect on hCG induced cyclic AMP secretion. 5, 8, 11, 14 Eicosatetraynoic acid (ETYA), a general inhibitor of AA metabolism, and Nordihydroguaiaretic acid (NDGA), an inhibitor of the lipoxygenase pathway of AA metabolism, inhibited hCG induced T secretion while indomethacin, an inhibitor of cyclo-oxygenase pathway, had no effect on hCG induced T secretion. We conclude from these data that AA plays a role in the regulation of hCG induced steroidogenic responses in rat Leydig cells and that the metabolite(s) of AA that are involved are not cyclooxygenase products.

5,8,11,14-Eicosatetraynoic Acid↗

Coordinate pattern of secretion of luteinizing hormone and testosterone in mature male turkeys under continuous and intermittent photoschedules.

Secretory patterns of luteinizing hormone (LH) and testosterone (T) were determined in sexually mature male turkeys housed under Continuous [14 h light (L): 10 h dark (D), n = 3)] or Intermittent [8 x (1L:2D), n = 3] photoschedules. Jugular vein cannulas were implanted on Day 0 and serial blood samples were taken at 5-min intervals for 12 h on Day 3 and again 4 to 7 d later. Most increases in T concentration were preceded by an increase in LH concentration for both photoschedules. Treatment differences for overall mean T [1.77 +/- .58 (SE) ng/mL], baseline T (.92 +/- .30 ng/mL), T peak number (6.1 +/- 1.2 per 12 h), T peak amplitude (2.77 +/- 1.70 ng/mL), or T peak length (79 +/- 24 min) were not significant (P > .05). The number of LH peaks was greater in the Continuous than Intermittent group (11.7 +/- .6 vs 6.8 +/- 1.4 per 12 h, P < .05), but there were no treatment differences in overall mean LH (4.56 +/- 2.09 ng/mL), baseline LH (4.10 +/- 2.11 ng/mL), LH peak amplitude (2.80 +/- .92 ng/mL), or LH peak length (15.9 +/- 3.1 min). There were no differences in T or LH concentrations between the photo- and scotophases in the continuous group, and pulses of both were seen in both phases in both lighting treatments. It was concluded that minor differences in patterns of LH secretion may occur between Continuous and Intermittent stimulatory lighting treatments in sexually mature male turkeys.

Animals↗

Possible testicular 3 beta-hydroxysteroid dehydrogenase deficiency in cryptorchid neonates.

In order to explain the impaired neonatal secretion of testosterone (T) in cryptorchid neonates, plasma levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), precursors of T, and T were measured in bilateral cryptorchid and control babies from the first to the 90th day of life. RIA of steroids was performed after plasma ether extraction and celite ethylen glycole column chromatography. In comparison to the neonatal period, plasma LH, dehydroepiandrosterone (DHA), and T were increased in both groups at the 60th day, although cryptorchids showed significantly lower T level (1018 +/- 168 pg/ml) than controls (1985 +/- 410 pg/ml, p less than 0.001). At the same time, androstenedione (A) and 17 alpha-hydroxy-progesterone (17P) remained unchanged. Dihydrotestosterone (DHT) concentrations were higher in cryptorchids in the neonatal period, and increased in both groups at the second to third month of life. The T/DHT ratio was significantly higher in cryptorchids in all age groups. These data indicate that (1) neonatal T formation probably occurs through the delta 5 pathway; (2) impaired T secretion in cryptorchid neonates could be due to a deficiency of 3 beta-hydroxysteroid dehydrogenase; and (3) cryptorchid neonates exhibit an elevated 5 alpha-reductase activity of unknown origin.

3-Hydroxysteroid Dehydrogenases↗

Characterization of adrenergic control of the Leydig cell steroidogenesis: identification of both stimulatory and inhibitory components.

Percoll-purified Leydig cells were studied in vitro in order to evaluate the effect of adrenaline on testosterone (T) secretion. Adrenaline enhanced the basal and potentiated the hCG-induced T release. A similar effect was also obtained with the beta 2-agonist, salbutamol. Although phenylephrine, an alpha 1-agonist, did not alter the basal T secretion, it enhanced hCG-mediated T secretion. Para-aminoclonidine, an alpha 2-agonist, decreased the basal T release without altering the hCG-stimulated T release. These data demonstrate that either inhibitory or stimulatory effects on T release can be obtained and that they depend on the adrenoreceptor subtype involved.

Animals↗

[Long-term and late results of treatment in patients with a history of testicular torsion].

Testicular torsion is a surgical urgency. It may lead to loss of that organ and moreover, as revealed by experimental studies and clinical findings in adults, induces autoimmunological reactions with subsequent male infertility. To elucidate these sequellae the following questions seem to be relevant 1. Are there any antisperm antibodies or shifts in T cell CD4+, CD8+ and NK subpopulations in boys with a history of testicular torsion? 2. Is production of antisperm antibodies initiated and maintained in childhood, and amplified after puberty? 3. Does the age at testicular torsion and duration of exposure to sperm antigens/testicular tissue have an effect on induction and levels of antisperm antibodies? 4. Is hormonal function of testis/testes and gonadotropic activity of the pituitary gland normal in these patients? 5. What conditions (duration, subjective and objective symptoms) are associated with testicular torsion; what kind of intraoperative findings can be expected; what is the influence of testicular torsion on the twisted testis? The study group (GB) consisted of 37 boys and men aged from 8 months to 27 years (mean 12.3 years) recruited from 86 patients seen for testicular torsion at the Department of Pediatric Surgery, Pomeranian Academy of Medicine in Szczecin, between 1967 and 1992. The control group (GK) comprised 42 healthy boys and men aged 3 to 33 years (mean 12.1 years) (Tab. 1). The analysis was based on: 1) clinical files; 2) follow-up results; 3) laboratory findings; 4) statistics. According to clinical data and physical examination, testicular torsion usually appeared during puberty, neonatal period and infancy and the mean duration of torsion was 12.4 days. The best prognosis for salvage of the twisted testis was for torsions lasting no longer than 8 hours. Only 8 of 37 twisted testes could be salvaged (including 4 hypotrophic testes; Tab. 2). There were 21 positive ELISA tests (level of antisperm antibodies exceeding 2 fg/pl) in the study group (mean 4.45 +/- 5.6 fg/pl), including 13 boys with testicular torsion in the prepubertal age and 8 during puberty (Tab. 3). A tendency to higher levels of antibodies with age was observed. In the control group there were 35 negative and 7 positive results (mean 1.05 +/- 1.86 fg/pl) (Tab. 4), significantly less than in the study group (p < 0.001). Trend curves (Fig. 1) and Pearson's correlation coefficients (Fig. 2) for levels of antibodies and age at presentation of testicular torsion were established for both groups. Mean percentages of CD4+, CD8+ and NK cells (indirect immunofluorescence test with monoclonal antibodies) were insignificantly lower in the study group (Fig. 3). Shifts in favor of CD4+ and NK subpopulations found in some patients correlated with high levels of antisperm antibodies (Tab. 5 and Fig. 4). Elevated LH and/or FSH (21 patients) and/or testosterone levels (13 patients) were usually observed during puberty (Tab. 6). The results indicate that antisperm antibodies are detected in more than half of the boys with a history of testicular torsion. This is accompanied in some cases by shifts in CD4+ and NK lymphocyte subpopulations correlating with high antibody levels. Production of antisperm antibodies initiated during prepuberty (in infancy or even in the neonatal period) persists and is amplified after puberty due to increasing amounts of antigen material. Age at testicular torsion (age at potential exposure to spermatic antigens/testicular tissue from the twisted or de-twisted testis with severe haemorrhagic lesions or left in the abdominal cavity) has an effect on the future production and levels of antisperm antibodies. Disturbances in the secretion of LH and/or FSH were observed in 2/3 of the boys/men with a history of testicular torsion. Abnormal secretion of testosterone was found in 1/3 of the patients. These hormonal disorders seem to have no influence on virilization, libido or sexual potency.

Adult↗

Inhibition of testicular steroidogenesis in 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated rats: evidence that the key lesion occurs prior to or during pregnenolone formation.

The mechanism by which 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) treatment decreases testosterone (T) secretion without significantly altering plasma luteinizing hormone (LH) concentrations was investigated. Testes from sexually mature Sprague-Dawley rats dosed 7 days earlier with 100 micrograms TCDD/kg secreted 30-75% less T than did testes from control rats when perfused in vitro with the LH analog human chorionic gonadotropin (hCG). This decrease confirms that testicular responsiveness to LH, the hormone which regulates T secretion in vivo, is impaired by TCDD treatment. Because TCDD also reduced intratesticular T content, the decrease in T secretion is due to an inhibition of T synthesis rather than to a failure of the secretion process. These effects of TCDD are not secondary to undernutrition, because perfused testes from feed-restricted control rats were fully hCG responsive. TCDD treatment neither increased the hCG-stimulated secretion of any T precursor nor significantly decreased the efficiency with which testes converted the pregnenolone (PREG) they synthesized into T (PREG is the initial steroidogenic intermediate). In addition, TCDD did not inhibit T secretion when steroidogenesis was supported by exogenous PREG at approximately the in vivo rate. We conclude that TCDD does not inhibit the conversion of PREG to T. The inhibition of T biosynthesis must instead result from an inhibition of PREG formation. The finding that TCDD treatment substantially decreased the rate at which hCG-perfused testes secreted PREG and its metabolites (a decrease seen across all hCG concentrations) confirms this conclusion. This inhibition of LH/hCG-stimulated PREG formation by TCDD must be due to a reduction in the activity of the enzyme which converts cholesterol to PREG (cytochrome P450scc), and/or an impairment in the multistep process responsible for mobilizing cholesterol to this enzyme.

Animals↗