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PubMed1985

Morphological and functional characteristics of rat Leydig cells isolated on Percoll gradients: is Leydig cell heterogeneity in vitro an artifact?

Rat testicular intertubular cells have been isolated on Percoll density gradients. Detailed light and electron microscopic studies have determined the sedimentation positions for Leydig cells, macrophages, fibroblasts, endothelial cells, germ cells and residual bodies. Stereological techniques have been utilized to determine the number of cells in the region of the gradient where Leydig cells sediment. Morphologically intact Leydig cells were present in the more dense region of the gradient (1.0590-1.0900 g/ml), and they responded to hCG stimulation with an 11-fold increase in testosterone production and contained LH/hCG receptors. Leydig cells in the less dense region of the gradient (1.0440-1.0589 g/ml) secreted less testosterone and contained less hCG receptors than those obtained from denser regions. However, the morphological studies described herein provide evidence for the first time that the majority of these less functional 'Leydig cells' from the lighter region of the gradients do not contain a nucleus and represent pieces of Leydig cell cytoplasm with variable size, shape and complement of organelles.

Animals↗
PubMed1988

Corpus luteum progesterone secretion in rats undergoing pineal-mediated reproductive regression.

In nonseasonal breeders, such as the laboratory rat, the potentiation of the antigonadal action of light deprivation by olfactory bulbectomy is manifested, among other things, by a diminished secretion of testosterone in males and estradiol in females. Little is known about the actions of the pineal gland on progesterone secretion. Since secretion of the luteotrophic hormones (LH and PRL) decreases in blind-anosmic rats and because the rat corpus luteum exhibits different degrees of LH and/or PRL dependency, the purpose of these experiments was to study the corpus luteum progesterone secretion in both pseudopregnant and pregnant blinded-bulbectomized rats. Female rats blinded and bulbectomized at the age of 25 d showed at adulthood (75 d old) (1) estrous cycles longer than the regular 4-5 d in length exhibited by intact rats: 82.3 vs. 9.0% (P less than .01); (2) a decreased paired ovarian weight, 24.1 +/- 3.7 (nine) vs. 37.3 +/- 2.2 (ten) mg/100 gm BW (P less than .05), and lower plasma levels of LH on metestrus: 15.9 +/- 1.7 vs. 26.2 +/- 3.4 ng/ml (P less than .01). Pinealectomy, as previously reported, completely reversed the effects of dual sensory deprivation. In contrast to the clear antigonadal action of the pineal gland, which seems to affect the follicular component of the ovary through modifications in the rate of LH secretion, the production of progesterone by the corpus luteum remained almost unaffected. Although the duration of the diestrous phase in both pseudopregnancy and pregnancy was significantly longer in blind-anosmic rats than in intact ones (P less than .01), the serum levels of progesterone throughout both corpus luteum phases were identical.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Ovine follicular fluid suppresses the ovarian secretion of androgens, oestradiol and inhibin.

An experiment was conducted to examine the effect of steroid-free ovine follicular fluid (oFF) on ovarian hormone secretion. Eight Merino x Finnish Landrace ewes in which the left ovary and vascular pedicle had been autotransplanted to a site in the neck were studied during the breeding season. Luteal regression was induced in all animals by injection of cloprostenol (100 micrograms, i.m.) on day 10 of the luteal phase. Four of the eight animals were treated with steroid-free oFF (3 ml, s.c.) in the early follicular phase, 24 and 36 h after injection of cloprostenol. Samples of both ovarian and jugular venous blood were collected at 4-h intervals from 20 h before until 96 h after injection of cloprostenol. Ovarian and jugular venous blood samples were also collected at 10-min intervals from 48 to 52 h after injection of cloprostenol to investigate the pattern of pulsatile secretion of ovarian hormones. Samples were assayed for oestradiol, androstenedione, testosterone and inhibin and the ovarian secretion rates calculated. Both injections of oFF resulted in a fourfold increase in the concentration of inhibin in jugular venous plasma within 4-8 h of administration (P less than 0.01) with concentrations remaining increased (P less than 0.05) until 56 h after cloprostenol (32 h after the first oFF injection). Following oFF injection there was a profound (100%; P less than 0.001) and prolonged decrease in the peripheral concentration of FSH until 60 h after cloprostenol at which time the concentration of FSH increased five- to sixfold (P less than 0.001) to a peak lasting 24 h. In contrast to FSH, the concentration of LH in jugular venous plasma rose immediately following oFF treatment and continued to increase, exhibiting a profile similar to that described for FSH. No preovulatory LH surge was detected in any of the oFF-treated ewes while untreated ewes had an LH surge within 58.0 +/- 1.2 (S.E.M.) h. Within 8 h of the first injection of oFF the ovarian secretion rate of oestradiol, androstenedione and inhibin began to decline to reach a nadir of less than 1 ng/min within 32-36 h (56-60 h after cloprostenol; P less than 0.01). Testosterone secretion, already barely detectable, did not change significantly following injection of oFF but remained low for 36 h following oFF and did not exhibit the increase observed over this period in controls. After injection of oFF the episodic secretion of oestradiol, androstenedione, testosterone and inhibin was markedly suppressed in spite of numerous pulses of LH.(ABSTRACT TRUNCATED AT 400 WORDS)

Androstenedione↗
PubMed2001

Testosterone deficiency and replacement.

In the human male, testosterone is the major circulating androgen. More than 95% of circulating testosterone is secreted by the testis with a production rate of 6-7 mg/day. The clinical effects of androgens are numerous, and testosterone deficiency is associated with a number of clinical abnormalities. Overt hypogonadism results in reductions in bone mineral density, alterations in body composition and effects on mood, aggressive behaviour, cognitive function, sexual function and several factors important for cardiovascular risk. Androgen replacement in this context is clearly beneficial, and numerous studies have demonstrated improvements in bone and muscle mass, reductions in body fat, and positive effects on quality of life following treatment. The benefits of therapy in men with milder degrees of hypogonadism, and elderly men with "physiological" testosterone deficiency, are less clear-cut, and the appropriate biochemical cut-off below which replacement should be offered has not been clearly defined. Several options are available for androgen replacement in adult men. Oral testosterone, intramuscular injections, subcutaneous implants and transdermal therapy have all been used. Each mode of delivery has advantages and drawbacks and the choice between them will often depend on patient reference. Recent advances include the development of longer-acting intramuscular preparations, which offer more stable androgen levels with fairly infrequent injections, and testosterone gel which appears to provide transdermal replacement without a high incidence of skin reactions. This article will examine the evidence concerning the impact of male hypogonadism and the response to androgen therapy. The question of who to treat will be addressed with particular reference to mild hypogonadism and hypogonadism in the elderly. Finally, an overview of the different modes of replacement therapy will be presented.

Behavior↗
PubMed1991

The effect of 6 weeks of testosterone treatment on pulsatile luteinizing hormone secretion in eugonadal female-to-male transsexuals.

Polycystic ovary disease generally is associated with elevated androgen levels and elevated luteinizing hormone (LH) levels, whereas follicle-stimulating hormone (FSH) levels are (sub)normal. To assess the role of androgens on gonadotropin secretion, we investigated the effect of 6 weeks of testosterone (T) undecanoate, 120 to 160 mg/d orally, on the parameters of the pulsatile secretion of LH in a group of six eugonadal female-to-male transsexuals with normal menstrual cycles. The treatment suppressed menstrual activity in all patients. Serum T and estrone were significantly elevated after treatment with oral T undecanoate. The parameters of the pulsatile secretion of LH were not affected by androgen administration. Levels of FSH, estradiol, and progesterone also did not change significantly.

Estrone↗
PubMed1987

Hirsutism, polycystic ovarian disease, and ovarian 17-ketosteroid reductase deficiency.

We studied an 18-year-old woman with progressive hirsutism, secondary amenorrhea, and polycystic ovarian disease. Excess androstenedione was secreted by the ovaries, most likely because of a genetic deficiency of ovarian 17-ketosteroid reductase, the enzyme that converts androstenedione to testosterone. Markedly elevated basal plasma levels of androstenedione, estrone, and testosterone were regulated by gonadotropin but not by ACTH. The rate of androstenedione production in the patient's blood at base line and after administration of dexamethasone was very high (10.0 to 11.6 mg per day; value in control women with hirsutism, less than 4.1 mg per day), whereas her blood production of testosterone was 0.64 to 0.7 mg per day, similar to or higher than that in control women with hirsutism. The fractional blood conversion ratio of androstenedione to testosterone was normal (5.6 percent). Thus, 88 to 93 percent of the testosterone in the blood was derived from the peripheral conversion of androstenedione, and very little testosterone was secreted by the ovaries. These in vivo biochemical data suggest that the patient had a deficiency of ovarian 17-ketosteroid reductase activity but normal pubertal activity. The patient's two younger sisters with peripubertal symptoms of androgen excess also had elevated serum levels of androstenedione. We propose that the increased secretion of androstenedione in the three siblings in this family was probably due to a genetic deficiency of ovarian 17-ketosteroid reductase.

17-Hydroxysteroid Dehydrogenases↗
PubMedDate not supplied

Valproate irreversibly alters steroid secretion patterns from porcine follicular cells in vitro.

The aim of the present study was to investigate whether exposure of porcine ovarian follicular cells to clinically relevant concentrations of valproate affected steroid production in vitro and to which extent these effects were reversed by removal of the drug from the culture medium. Small and medium follicles were obtained from ovaries collected, respectively, at days 8-10 and 14-16 of the estrous cycle. Theca and granulosa cells were collected from follicles and co-cultured in one well. To show whether the effect of valproate was reversible, cells were cultured for 24, 48, or 72 h with valproate 100 or 250 microg/ml. The medium was then changed to fresh medium without drugs for an additional 24, 48, or 72 h. Valproate added to the culture medium caused a significant reduction of estradiol secretion with concomitant increase in both testosterone and progesterone secretion by small follicles. In medium-sized follicles, 100 microg/ml valproate was without effect on estradiol secretion while 250 microg/ml caused a small, but statistically significant decrease. The effects of valproate on steroid secretion patterns were irreversibly independent of concentration, exposure time, and time of restoration after drug exposure up to 72 h in both small and medium follicles. In conclusion, the present study demonstrated that even short-term valproate treatment disrupted follicular steroidogenesis in isolated ovarian follicular cells resulting in increased testosterone and progesterone and decreased estradiol secretion. It was not possible to reverse the steroidogenic effects of valproate by removing the drug from the cell cultures.

Animals↗
PubMed1987

Onset of steroidogenesis and differentiation of functional LH receptors in rat fetal testicular cultures.

The present study was performed to investigate in vitro the onset of steroidogenesis and the responsiveness to LH in rat fetal testes. The male gonads explanted on days 12.5, 13.5, and 14.5 of gestation in M199 produced testosterone from 15.5 days as is the case in vivo dcAMP (1 mM) induced an anticipated steroidogenesis on day 14.5 with secretions of testosterone (0.026 +/- 0.003 ng/gonad/24 h) and progesterone (0.078 +/- 0.005 ng/gonad/24 h), whereas LH (100 ng/ml) has no effect. Antiandrogens such as aminoglutethimide (2 mM), cyproterone acetate (1 microgram/ml), and hydroxyflutamide (1 microgram/ml) could not delay the responsiveness to LH on day 15.5. An anticipated production of testosterone on day 14.5 in presence of DHA (200 ng/ml) could not induce functional LH receptors. It would appear that: (a) the onset of testosterone production occurs without extrinsic stimulatory factors; (b) dcAMP initiates an early steroidogenesis; (c) the onset of functional receptors is likely free of the androgenic environment.

Aminoglutethimide↗
PubMed1988

[Effects of bromocriptine on endocrine environment in the polycystic ovary syndrome].

In order to investigate the hormone feature and the effect of bromocriptine on endocrine profile in patients with polycystic ovary syndrome (PCO), twenty-four-hour secretion pattern of LH, FSH, PRL and testosterone were assessed in 8 PCO patients and 4 normal women as controls by obtaining serial blood samples, taken through a forearm cannula, at 30 minute intervals for 24 hours. Bromocriptine, 5 mg/day was given and 3 patients were reassessed in the follicular phase of the menstrual cycle after ovulatory periods were established during bromocriptine therapy. There was significant difference in pulse amplitude, but not in pulse frequency of LH and testosterone between PCO and normal women (23.1 +/- 9.49 vs 5.75 +/- 1.28 mIU/ml, p less than 0.01; 27.8 +/- 10.1 vs 10.2 +/- 2.63 ng/dl, p less than 0.01), and the 24 hour mean LH and testosterone levels were higher (p less than 0.01) in PCO (52.3 +/- 20.1 mIU/ml, 105.1 +/- 15.9 ng/dl) than in normal women (13.4 +/- 4.31 mIU/ml, 54.3 +/- 13.3 ng/dl). Though a pulsatility in FSH secretion was identified, no difference between normal women and PCO was observed. Mean PRL level was within the normal range in PCO but with a higher pulse frequency (p less than 0.01) and lower pulse amplitude (p less than 0.01) than those of the normal women. Furthermore, LH and testosterone secretions maintained the circadian changes in PCO patients against the normal women. During bromocriptine therapy, mean level and pulse amplitude of LH and testosterone were significantly suppressed, without changing in pulse frequency, whilst PRL secretory patterns were not reestablished. In conclusion we have found that PCO is associated with high level and pulse amplitude of LH and testosterone, with high frequency and low amplitude of PRL, and bromocriptine administration can blunt LH, PRL and testosterone secretion, suggesting a hypothalamic intervention in gonadotropic regulation in patient with PCO. In addition, the degree of bromocriptine to inhibit LH secretion might be related to the dose or duration of its administration, or to the sensitivity of the patients. The mechanism of bromocriptine for marked LH suppression in PCO patients remains to be elucidated.

Adult↗
PubMed1998

Isolated porcine ovarian follicles as a model for the study of hormone and growth factor action on ovarian secretory activity.

The aim of our in vitro experiments with isolated porcine ovarian follicles was to study the effects of gonadotropins, GH, IGF-I and oxytocin (OT) on release of ovarian steroid, OT, IGF-I, insulin-like growth factor-binding protein-3 (IGFBP-3), prostaglandin F (PGF), prostaglandin E (PGE) and cAMP. It was found that quarters of ovarian follicles cultured for 8 days produced significant amounts of progesterone, estradiol-17 beta, OT and IGFBP-3 with peaks of accumulation from the 3rd to the 8th day of culture. Addition of serum promoted progesterone, estradiol and OT release, whilst accumulation of IGFBP-3 was maintained to a greater extent in serum-free medium. GH (10 ng/ml or above) was able to inhibit androstenedione, OT, PGF and IGFBP-3, to stimulate IGF-I and cAMP, and to alter testosterone and PGE release by follicles cultured in serum-supplemented and/or serum-free medium. IGF-I (10 ng/ml or more) inhibited androstenedione and PGF secretion, stimulated testosterone, estradiol, OT and cAMP production, but did not influence progesterone, IGFBP-3 or PGE output in these conditions. OT (100 ng/ml) was able to inhibit androstenedione and to stimulate testosterone, IGF-I, PGF and PGE, but not estradiol or IGFBP-3 release. A stimulatory effect of LH on progesterone and OT and an inhibitory influence of LH on estradiol secretion in the serum-supplemented medium were observed. FSH in these conditions stimulated OT, but not progesterone or estradiol secretion. The use of this experimental model suggests the involvement of gonadotropins, OT, GH and IGF-I in the control of ovarian steroid and nonapeptide hormone, growth factor, growth factor-binding protein, prostaglandin and cyclic nucleotide production. The stimulatory effect of GH on IGF-I, and the stimulatory influence of IGF-I on OT, as well as coincidence of the majority of effects of IGF-I and OT, suggest the existence of a GH-IGF-I-OT axis. On the other hand, the different patterns of action of GH and IGF-I on OT, estrogen and IGFBP-3 suggest that part of the GH effect on ovarian cells is IGF-I independent.

Androstenedione↗
PubMed1977

Diurnal variations of serum testosterone levels in intact and gonadectomized male and female rhesus monkeys.

A radioimmunoassay for serum testosterone which does not require chromatographic separation was used to measure the diurnal variations in intact and orchidecomized males and intact and ovariectomized females. The intact male rhesus monkey shows a distinctive diurnal variation in serum levels of testosterone characterized by lower values during the day and a marked increase in the early evening (1900-2200 hr). The testosterone levels remain high throughout most of the lights-off period in the intact male. In contrast to the intact male, the markedly lowered serum levels of testosterone in the orchidectomized male were higher during the day and consistently showed a nadir during the early evening (2000-2200 hr). The evening nadir of testosterone levels was 51.0% lower than the 24-hr mean whereas the maximum serum level was 46.4% higher. A similar circadian pattern of testosterone was seen in both the intact and ovariectomized females. The testosterone values were higher during the day and consistently showed a nadir during the early evening. These results suggest that the adrenal secretion of testosterone varies in a diurnal pattern characterized by an early evening nadir. This adrenal pattern is overshadowed by a much larger gonadal rhythm in the intact male.

Animals↗
PubMed1982

Testosterone concentration within the tunica vaginalis of boys and adult men.

The testosterone level in fluid contained in the tunica vaginalis has been determined in 25 adult men referred for infertility and in 20 boys aged 0-10.5 years operated on for hydrocele. The median concentrations of testosterone were found to be 392 nmole/1 (range 78-957) and 1.1 nmole/1 (range 0.16-182), respectively. The median value for adult men was 20 times the concentration of testosterone found in the peripheral blood of that group while the median value for the boys was 4 times that found in their peripheral blood. It is concluded, firstly, that the high level of testosterone in the peritesticular space of adult men strongly indicates that diffusion of testosterone through the testicular capsule does take place. Secondly, testosterone levels in fluid from the peritesticular space which significantly exceeds those in peripheral blood in prepubertal boys furnishes evidence of testicular secretion of testosterone in that age group. Consequently, the peritesticular tissues such as the epididymis, gubernaculum and scrotum are exposed to quantities of testosterone far exceeding those brought by the general circulation.

Adult↗
PubMed1996

Cytokines derived from activated human mononuclear cells markedly stimulate transferrin secretion by cultured Sertoli cells.

There is considerable evidence that Sertoli cell function is controlled not only by hormones, but also by locally produced growth factors and cytokines. To gain more insight into the nature and effects of cytokines potentially involved in the control of Sertoli cell function, we incubated rat Sertoli cells with media conditioned by activated human peripheral blood mononuclear cells. Such media (PBMC-CM) are known to be an extremely rich source of a variety of cytokines. It was demonstrated that PMBC-CM and protein fractions derived from them stimulate Sertoli cell transferrin secretion and messenger RNA production more potently then peritubular cell-conditioned medium or FIRT (a combination of FSH, insulin, retinol, and testosterone). Transferrin secretion expressed per mg cell DNA was stimulated approximately 5-fold by peritubular cell-conditioned medium or FIRT and nearly 20-fold by PBMC-CM. The effects of PBMC-CM were accompanied by a limited increase in cAMP and a noticeable rise in cGMP. Affinity chromatography on a column coated with an antiserum directed against interleukin-1 beta (IL-1 beta) showed that part of the activity in the PBMC-CM was related to IL-1 beta. The remainder of the activity was largely retained by an affinity column coated with an antiserum that recognizes IL-6 and a number of other known and unknown cytokines. Purified IL-1 beta provoked a 2- to 3-fold stimulation of Sertoli cell transferrin secretion. More limited stimulatory effects were observed with IL-6. Neither of these cytokines or their combination approached the degree of stimulation observed with crude PBMC-CM, suggesting that other cytokines are involved. It is concluded that the mixture of cytokines present in PBMC-CM is a more powerful stimulator of Sertoli cell transferrin secretion than any other agonist known at the present time. IL-1 and IL-6 may be responsible for part of the observed effects, but one or more other cytokines are probably involved.

Animals↗
PubMed1995

Expression and regulation of steroid 5 alpha-reductase in the urogenital tract of the fetal rat.

Two androgens, testosterone and dihydrotestosterone, are required for the development of the male urogenital tract in the rat. Testosterone is secreted by the fetal testes and is thought to elicit differentiation of the Wolffian ducts into seminal vesicles, vas deferens, and epididymides. Testosterone is converted into dihydrotestosterone by steroid 5 alpha-reductase in the urogenital tract, and this conversion is necessary for the differentiation of the prostate and external genitalia. Genes encoding two 5 alpha-reductase isozymes, designated type 1 and type 2, have been identified. We examined the expression and regulation of these genes on days 17-21 in the urogenital tracts of male and female fetuses. Expression of the type 1 gene predominated in epithelial cells, whereas type 2 gene expression was limited to mesenchymal cells. Surprisingly, this expression pattern was detected in both testosterone-dependent and dihydrotestosterone-dependent anlagen of the urogenital tract and was the same in both male and female fetuses. Furthermore, transcripts encoding the two isozymes were present in their respective cell types before the overt differentiation of internal genitalia. Androgens stimulated expression of the type 2 gene in the urogenital tracts of both sexes, but did not effect expression of the type 1 gene or the cell type-specific expression patterns of the 5 alpha-reductase genes. In the adult prostate, 5 alpha-reductase gene expression is under feedforward control, in which the product of the enzyme, dihydrotestosterone, stimulates the expression of the gene. However, no evidence for feedforward regulation of either 5 alpha-reductase gene was detected in the fetus.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1988

Effects of chronic infusions of sex steroid-binding protein on the testosterone-mediated inhibition of gonadotropin secretion and maintenance of sex accessory glands in male rats.

Sex steroid-binding protein (SBP) is a plasma glycoprotein which, in man and many other mammals, binds significant amounts of circulating testosterone (T) with high affinity. To evaluate the effects of T binding by SBP on the control of reproductive function in males, SBP was purified from human plasma and administered by chronic infusion to castrated T-treated rats, animals that lack endogenous SBP. Plasma T concentrations in males implanted with 20-mm T capsules and infused with vehicle for 48 h were maintained at 1.37 +/- 0.14 ng/ml, and plasma LH and FSH concentrations remained at intact levels. Castrates implanted with identical T capsules but infused with human (h) SBP at a rate that produced a steady state plasma hSBP concentration of 75 nM, had markedly higher plasma T concentrations (3.44 +/- 0.32 ng/ml); however, circulating LH and FSH concentrations were not significantly different from those of the vehicle-infused controls. Similarly, the pituitary LH response to a bolus injection of LHRH was not affected by hSBP infusions. Measurements of tissue concentrations of T, dihydrotestosterone, and 3 alpha-androstanediol in the ventral prostate and seminal vesicles, as well as the weights of these organs, failed to reveal any effects of hSBP infusions on the uptake, metabolism, or action of T. Analysis of T distribution in plasma showed that the hSBP infusions produced marked increases in total plasma T levels but resulted in only marginal reduction in the concentration of T not bound to hSBP. These results are consistent with the hypothesis that T not bound to SBP is the major feedback-effective moiety and that under conditions of constant release of T into the circulation, an increase in plasma T binding by SBP increases the total plasma T concentration but does not appear to significantly alter the feedback-effective levels of T in the circulation. Therefore, it would appear that moderate changes in the amount of high affinity binding of T in the circulation would have little, if any, effect on androgen balance in adult males.

Animals↗
PubMed2002

Effects of propyl paraben on the male reproductive system.

Parabens are p-hydroxybenzoic acid ester compounds widely used as preservatives in foods, cosmetics, toiletries and pharmaceuticals. These compounds exert a weak estrogenic activity as determined by in vitro estrogen receptor assay and in vivo uterotrophic assay. In a previous study, it was demonstrated by the present author that exposure of post-weaning mammals to butyl paraben adversely affects the secretion of testosterone and the function of the male reproductive system. In the present study, it is shown that propyl paraben also adversely affects the hormonal secretion and the male reproductive functions. Propyl paraben was administered to 3-week-old rats which were divided into four groups of eight animals each, at doses of 0.00, 0.01, 0.10 and 1.00% with the AIN93G modified diet. At the end of 4 weeks, the rats were sacrificed by decapitation and the weights of testes, epididymides, prostates, seminal vesicles and preputial glands were determined. There were no treatment-related effects of propyl paraben on the organ weights in any of the study groups. The cauda epididymal sperm reserves and concentrations decreased in a dose-dependent manner and the difference was significant at dose of 0.10% and above. Daily sperm production and its efficiency in the testis of all groups receiving propyl paraben significantly decreased. The serum testosterone concentration decreased in a dose-dependent manner and the decrease was significant in the group that received the highest dose. The exposure level at which this effect was observed is the same as the upper-limit acceptable daily intake (10 mg/kg body weight/day) of parabens in the European Community and Japan.

Animals↗
PubMedDate not supplied

Stimulatory effect of lactate on testosterone production by rat Leydig cells.

Previously we found that the increased plasma testosterone levels in male rats during exercise partially resulted from a direct and luteinizing hormone (LH)-independent stimulatory effect of lactate on the secretion of testosterone. In the present study, the acute and direct effects of lactate on testosterone production by rat Leydig cells were investigated. Leydig cells from rats were purified by Percoll density gradient centrifugation subsequent to enzymatic isolation of testicular interstitial cells. Purified rat Leydig cells (1 x 10(5) cells/ml) were in vitro incubated with human chorionic gonadotropin (hCG, 0.05 IU/ml), forskolin (an adenylyl cyclase activator, 10(-5) M), or 8-bromo-adenosine-3':5'-cyclic monophosphate (8-Br-cAMP, 10(-4) M), SQ22536 (an adenylyl cyclase inhibitor, 10(-6)-10(-5) M), steroidogenic precursors (25-hydroxy-cholesterol, pregnenolone, progesterone, and androstenedione, 10(-5) M each), nifedipine (a L-type Ca(2+) channel blocker, 10(-5)-10(-4) M), or nimodipine (a potent L-type Ca(2+) channel antagonist, 10(-5)-10(-4) M) in the presence or absence of lactate at 34 degrees C for 1 h. The concentration of medium testosterone was measured by radioimmunoassay. Administration of lactate at 5-20 mM dose-dependently increased the basal testosterone production by 63-187% but did not alter forskolin- and 8-Br-cAMP-stimulated testosterone release in rat Leydig cells. Lactate at 10 mM enhanced the stimulation of testosterone production induced by 25-hydroxy-cholesterol in rat Leydig cells but not other steroidogenic precursors. Lactate (10 mM) affected neither 30- nor 60-min expressions of cytochrome P450 side chain cleavage enzyme (P450scc) and steroidogenic acute regulatory (StAR) protein. The lactate-stimulated testosterone production was decreased by administration of nifedipine or nimodipine. These results suggested that the physiological level of lactate stimulated testosterone production in rat Leydig cells through a mechanism involving the increased activities of adenylyl cyclase, cytochrome P450scc, and L-type Ca(2+) channel.

Animals↗