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PubMed1983

Effect of chlorpromazine on hypothalamic-pituitary-gonadal function in 10 adolescent schizophrenic boys.

Low basal plasma testosterone levels with normal response to human chorionic gonadotropin (HCG) stimulation and mild hyperprolactinemia and blunted luteinizing hormone (LH) response to luteinizing-releasing hormone (LRH) stimulation were found in 10 adolescent schizophrenic boys who had been treated with chlorpromazine for more than 6 months. These findings may indicate a disturbance of the hypothalamic-pituitary-gonadal function in these patients, probably due to the prolonged administration of chlorpromazine. It remains to be established whether the decrease in basal testosterone secretion is caused directly by chlorpromazine or secondarily by the drug-induced hyperprolactinemia.

Adolescent↗
PubMed2000

The effect of exposure to oestrous ewes on rams' sexual behaviour, plasma testosterone concentration and ability to stimulate ovulation in seasonally anoestrous ewes.

Previous research has shown that the proportion of seasonal anoestrous ewes that ovulate in response to the introduction of rams ('ram effect') is dependent upon pheromonal and sexual behavioural stimuli emitted by the rams. Close contact with oestrous ewes is likely to increase the rams' libido and level of testosterone secretion, which in turn has been suggested to positively influence the production of pheromones. Thus, the sexual stimulation of rams could be used to improve the efficacy of the 'ram effect'. In the present experiment, 272 ewes were introduced (1) to rams without recent experience of oestrous ewes, (2) to rams recently exposed to oestrous ewes, (3) and (4) to oestrous ewes and rams with or without recent experience with oestrous ewes, or (5) remained isolated from rams. Serum testosterone concentration of rams was elevated equally (P<0.05) when oestrous or anoestrous were introduced. Exposure to oestrous ewes before or after introduction increased (P<0.05) the various measures of ram sexual behaviour directed towards anoestrous ewes. However, there was no statistical evidence that increased sexual activity resulted in an improvement in the ability of rams to stimulate ovulation in anoestrous ewes.

Journal Article↗
PubMed1982

Effect of cimetidine o endocrine functions--prolactin.

Effects of cimetidine on the endocrine function were examined in 16 human subjects, i.e. 6 healthy adult volunteers, and each 5 male and female gastro-duodenal ulcer patients. They were all subjected to the examination on the fluctuation of prolactin (PRL) after one-shot intravenous injection of cimetidine. The peptic ulcer patients were orally given 800 mg/day of cimetidine for further 4 weeks. PRL, gonadotropins and sex hormones were determined in the male patients, and only PRL in the females patients. TRH-load test was carried out in all the ulcer patients before and after the administration of cimetidine. The results are shown below: 1) After one-shot intravenous administration of cimetidine 200 mg, serum-PRL significantly increased, the peak level, however, being within normal value range. The increase in PRL was transient, and recovered to the pretreatment value in 60-180 minutes after the administration. 2) During and after the repeated oral administration of 800 mg/day of cimetidine for the consecutive 28 days, serum PRL level did not significantly change. Neither was noted any influence on gonadotropin (LH, FSH) nor sex hormones (estradiol, testosterone) secretion. 3) PRL secretory functions at 500 microgram TRH loading were similar before and after oral administration of cimetidine, without difference in the reactivity.

Adult↗
PubMed1979

Presence of a human chorionic gonadotropin--like substance in human sperm.

An hCG-like material has been extracted from human sperm. These experiments were designed to characterize this material. Sperms of 10 volunteers were separated from seminal fluid, washed in PBS three times, and resuspended in 0.5 ml of the same buffer. Samples were pooled; cells were disrupted by sonication and extracted in alkaline buffer by constant agitation at 4 degrees C. The extract was ultracentrifuged at 4 degrees C. Supernate was lyophilized and reconstituted in 2 cc of distilled water. This material presented a dose-response curve parallel to those of IS2-hCG and CR119 in beta hCG RIA. When chromatographed in a Sephadex G-150 column the extract eluted within the hCG range and immunoreacted in the specific beta hCG RIA. When absorbed onto a concanavalin A--Sepharose column, all recovered immunoreactive material eluted after exposure to alpha-D-methylglucoside, indicating that it is a glycoprotein. The extract stimulated progesterone and testosterone secretion in porcine granulosa cells and decapsulated rat testis, respectively, indicating its biologic potency.

Adenylyl Cyclases↗
PubMedDate not supplied

Cadmium-induced damage to primary cultures of rat Leydig cells.

The mechanism of testicular toxicity of cadmium is poorly understood. Previous studies focusing on cadmium-related changes in testicular histopathology have implicated testicular blood vessel damage as the main cause of cadmium toxicity. To further explore the toxic effects of cadmium on testis, we isolated and cultured rat Leydig cells, exposed to 10, 20, and 40 microM of cadmium chloride (base doses). After 24 h of exposure, cells and supernatants were harvested to examine cytotoxicity and genotoxicity of cadmium. The results show that both cell viability and concentration of testosterone excretion in primary Leydig cells are significantly lower in cadmium-exposed groups compared to the controls. Changes in testosterone excretion with human chorionic gonadotropin (hCG) stimulation is especially profound. The contents of malondialdehyde (MDA) and the activity of glutathione peroxidase (GSH-Px) in exposed groups are significantly higher than those in the control group, but the activity of superoxide dismutase (SOD) is lower. The number of cells with DNA single strand breaks and the levels of cellular DNA damage in all three exposure groups are significantly higher than in controls. These results indicate that cadmium is directly toxic to primary Leydig cells, and that the decreased percentage of normal cells and the increased level of DNA damage in cadmium-exposed Leydig cells may be responsible for decreased testosterone secretion.

Animals↗
PubMedDate not supplied

Comparison of biological effects of a sustained delivery system and nonencapsulated LH-RH antagonist SB-75 in rats.

Recently, we developed long-acting microcapsules and microgranules of the LH-RH antagonist SB-75. In this study, we compared the inhibitory effects of a single injection of encapsulated and nonencapsulated LH-RH antagonist SB-75 on gonadotropin and testosterone secretion. The resulting serum SB-75 levels were also measured by RIA. Microgranules containing 4% of this antagonist in poly(DL-lactide-co-glycolide) were administered IM at two different doses (30 and 60 mg/rat) to male rats. Other groups of rats were injected SC with equivalent doses of nonencapsulated SB-75 (1.25 and 2.5 mg/rat). The administration of microgranules at a dose of 60 mg/rat produced a significant elevation of serum SB-75 until day 76, and serum testosterone and LH levels were suppressed below the detection limit of the RIA for a period of 70 days. An equivalent dose of nonencapsulated SB-75 acetate (2.5 mg/rat) produced a significant elevation of SB-75 levels for 20 days and decreased testosterone to castration values and LH levels for merely 21 days. In rats treated with 30 mg microgranules of SB-75 or an equivalent dose of SB-75 acetate (1.25 mg/rat), serum testosterone and LH were suppressed to a similar extent, but for only 2 weeks. In another study, the effect of a single SC injection of 1.25 mg/rat of antagonist SB-75 on pituitary LH-RH receptors was determined, 7 and 60 days after administration. SB-75 produced a significant (p < 0.01) downregulation of membrane receptors for LH-RH 7 days after administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Alterations in mitogenic and steroidogenic activities in rat testicular interstitial fluid after administration of ethane dimethane sulphonate.

A single dose of EDS was given to mature male rats and interstitial fluid (IF) was collected to determine the potency of mitogenic and steroidogenic activities therein. The potency of the factor stimulating testosterone secretion in vitro by Percoll-purified Leydig cells was significantly elevated 2 weeks after EDS, whilst the potency of mitogenic activities (stimulation of DNA synthesis by BALB/c 3T3 cells) was not elevated until 4 weeks after EDS treatment. This study suggests that two separate factors, one with mitogenic and the other steroidogenic activity, may be involved in the response of Leydig cells after EDS administration. The mitogenic factor may play a role in Leydig cell regeneration whereas the testosterone-stimulating factor may be involved in testicular testosterone homeostasis.

Animals↗
PubMed1995

Involvement of a direct neural mechanism in the control of gonadal functions.

Much time has been devoted to study of the hypothalamo-hypophyseal-gonadal axis. However, there is now evidence of a complementary control mechanism for the gonads, namely a pituitary-independent, direct neural link that exists between the central nervous system and the gonads. We investigated whether mediobasal temporal lobe structures could control gonadal functions by a purely neural mechanism or whether they acted through the classical hypothalamo-hypophyseal system. Right- or left-sided deafferentiation of the temporal lobe was combined with right- or left-sided hemicastration in adult and prepubertal male and female rats. In adult females right-sided deafferentiation, regardless of the side of hemiovariectomy significantly reduced the extent of compensatory ovarian hypertrophy. Similar lesions on the left side did not interfere with the usual compensatory ovarian growth. This difference in compensatory hypertrophy between right- and left-sided lesioned rats was observed even in the face of a significant drop in serum LH concentrations in both groups. In pre- and postpubertal females temporal lobe lesion in either side was unable to alter compensatory hypertrophy or serum LH or progesterone concentrations. In adult male rats only left-sided deafferentiation combined with left orchidectomy resulted in decreased T production, while in prepubertal male rats, only right-sided brain surgery plus left orchidectomy resulted in a significant decrease in basal testosterone secretion of the remaining testis. These findings indicate that mediobasal temporolimbic structures are involved in the neural control of gonadal functions. It appears that this lateralized mechanism is age- and sex-dependent.

Animals↗
PubMed2001

Effects of the luteinising hormone-releasing hormone (LH-RH) agonist leuprolide on adenylyl cyclase regulation through G-protein coupled receptors in rat ventral prostate.

Luteinising hormone-releasing hormone (LH-RH) agonists are widely used for the therapy of advanced prostate cancer through the suppression of testosterone secretion. Furthermore, recent studies indicate the existence of prostate LH-RH receptors coupled to signalling pathways resulting in direct antiproliferative effects. In order to shed light on the mechanisms through which these compounds inhibit prostate cell growth, we investigated the effects of leuprolide (a LH-RH agonist) treatment of rats compared with the effects of surgical castration on the behaviour of G-protein coupled receptors acting through adenylyl cyclase in the ventral prostate. Important decreases of both plasma testosterone levels and ventral prostate weight were observed 5 weeks after subcutaneous (s.c.) injection of a leuprolide-depot preparation (1.5 mg/kg body weight (b.w.)) or 5 days after bilateral gonadectomy. However, leuprolide treatment increased the number of vasoactive intestinal peptide (VIP) receptors and the ability of this neuropeptide to stimulate adenylyl cyclase activity in prostate membranes, whereas surgical castration decreased both parameters. Moreover, leuprolide resulted in significant increases of prostate alpha(s) and alpha(i1-3) (but not alpha(i1) and beta) G-protein levels, while the four G-protein subunits were overexpressed after gonadectomy. The estimation of alpha(s) and alpha(i) activity by experiments with Gpp[NH]p and forskolin indicated a potentiation of the two arms of adenylyl cyclase regulation in leuprolide-treated rats. Present observations suggest that leuprolide treatment leads to an antimitogenic response by acting mainly through the activation of Gi proteins negatively coupled to adenylyl cyclase.

Adenylyl Cyclases↗
PubMed1983

Specificity to gonadotropins in the response of in vitro estrogen secretion by fish ovaries.

Gonadotropin preparations from three classes of tetrapods (amphibian, avian, and mammalian) and a chondrosteian and teleost fish were used to investigate the species specificity and hormonal (FSH/LH) specificity of in vitro steroid (estradiol-17 beta) production by the teleost ovary. Results for ovaries from one species of gobiid, Gillichthys mirabilis, and two cichlids, Cichlasoma citrinellum and Sarotherodon mossambicus, revealed a general lack of species specificity in the response to tetrapod gonadotropins, but the piscine, especially sturgeon, gonadotropins were much more potent than any of the tetrapod hormones. All three species of teleost ovaries responded to both types of tetrapod gonadotropins (FSH and LH), but the extent of hormonal specificity was variable. The gobiid ovary showed the highest LH specificity (potencies of FSHs = 7-14% of LH); in the two cichlids the potency of FSHs ranged from 11 to 100% of the respective LHs. In general, the specificity of the ovarian steroidogenic response to gonadotropins parallels that observed for testosterone secretion in the males of the same three fish, but the differential actions of the tetrapod hormones (both species and hormonal specificity) are more exaggerated for the testes.

Animals↗
PubMed1992

[The male climacteric from the practical viewpoint].

A transient physiologic period similar to that in women leads from full sexuality to senium in the life of men, too. This phase may involve the complex of male climacteric symptoms. The diminished testosterone secretion of the testes as endocrine "primum movens", together with an increased level of the carrier protein (SHBG), results in a reduced androgen supply of the organism, as reflected in a low free andorgenic index. The diagnosis of male climacteric is made on the basis of an enhanced serum LH level. With regard to the differential diagnosis, atherosclerosis, diabetes mellitus, chronic alcoholic liver damage, malignant tumors and prostatic complaints are particularly to be considered. The hormonal treatment consists of low-dose testosterone medication; for the prevention of osteoporosis, however, testosterone preparations may be replaced by anabolic steroids. As for women, the concomitant vegetative phenomena of the climacteric syndrome should be alleviated symptomatically.

Climacteric↗
PubMed1990

The interaction of Sertoli and Leydig cells in the testicular toxicity of tri-o-cresyl phosphate.

Previous studies have shown that after dosing with tri-o-cresyl phosphate (TOCP), the testis contains more active intermediate (saligenin cyclic-o-tolyl phosphate; SCOTP) than do other organs or blood. SCOTP is produced by a cytochrome P450-dependent reaction, and the Sertoli cells, although containing little P450, are the testicular cells that show the first signs of damage after TOCP administration. The present studies evaluated (i) whether testicular Leydig cell production of SCOTP might explain the elevated testicular concentration of SCOTP, (ii) if this production affected testosterone secretion, and (iii) if Sertoli cells cocultured over TOCP-exposed Leydig cells would show effects similar to those found after SCOTP exposure of Sertoli cells in vitro, indicating a cell interaction. Previous data showed that a target enzyme for SCOTP in Sertoli cells, nonspecific esterase (NSE), was inhibited by exposure in vitro to SCOTP, but not to TOCP. In the present experiments, HPLC analysis identified SCOTP in media from Leydig cells cultured with radiolabeled TOCP, demonstrating activation. TOCP addition to Leydig cells decreased testosterone output after stimulation with hCG, an effect that was replicated by subsequent in vivo experiments. Addition of various intermediates in the testosterone biosynthesis pathway indicated that both mitochondrial- and microsomal-based steps in the pathway were affected. Collectively, these data indicate that Leydig cells can activate TOCP. To model whether this activation might affect Sertoli cells in vivo, Sertoli cells were plated in culture-well inserts suspended above (cocultured with) isolated Leydig cells in the presence of TOCP. Sertoli NSE activity was diminished, while remaining unchanged when cultured in the presence of TOCP but without Leydig cells, or over Leydig cells alone. These results show that the Leydig cells in the testis are capable of activating TOCP to SCOTP, and that this can produce effects in Sertoli cells. This in situ activation of TOCP to SCOTP may help explain why the testis contains high concentrations of SCOTP after in vivo dosing with TOCP, and why the testis is a target organ for TOCP toxicity.

Androstenedione↗
PubMed2003

Congener-specific accumulation of polychlorinated biphenyls in ovarian follicular wall follows repeated exposure to PCB 126 and PCB 153. Comparison of tissue levels of PCB and biological changes.

OBJECTIVE: Small (SF), medium (MF) and large (LF) preovulatory porcine follicles were isolated and incubated in an Erlenmeyer flask containing 5 ml of medium with addition of PCB 126 or PCB 153 to test differences in their accumulation in the follicular wall. METHODS; The follicles were incubated in M199 medium at 37 degrees C with constant shaking at 70 rpm, for 6 days. The media were changed every day and repeated dose 25 pg/ml of PCB 126 or 25 ng/ml of PCB 153 was added each day till 6 days of culture. Media were collected every day and frozen for steroid analysis by RIA. 24 h after the last treatment follicles were frozen for further polychlorinated biphenyls (PCB) content analysis. PCB concentrations in the follicular wall were analysed by mass spectrometry. RESULTS: 3.3%; 3.6% and 5.6% of total PCB 126 dose, and 71%; 71.4% and 30.4% of total PCB 153 dose accumulated in SF, MF and LF follicles, respectively. The accumulative effect of PCB was manifested by the disruption of estradiol (E2) secretion. In SF antiestrogenic action of PCB 126 was observed during the whole time of exposure while PCB 153 decreased E2 till 4 days of culture and then estrogenic action was observed. In MF, both these congeners decreased E2 till 5 days of exposure and then estrogenic actions were noted with the highest magnification in the case of PCB 126. In LF both PCB studied increased E2 till 3 days of exposure with the highest magnification of PCB 126, then antiestrogenic action was noted. Testosterone secretion was generally affected in a pattern oposite to that of E2 suggesting action on P450arom activity. CONCLUSION: The results of these studies demonstrated that disruption of aromatization process in the follicles following repeated exposure to both congeners is not directly correlated with the bioaccumulation or amount of PCB within the follicular wall.

Animals↗
PubMed2001

Estradiol enhances the stimulatory effect of FSH on testicular maturation and contributes to precocious initiation of spermatogenesis.

Male rats were daily injected with human FSH (hFSH) or estradiol benzoate (EB) or hFSH+EB between day 5 and 15 of life and autopsied on day 16. hFSH accelerated testicular growth, increased number of spermatogonia and serum level of testosterone. hFSH stimulated also spermatogonia differentiation, which resulted in 5-fold increase of the number of spermatocytes. EB given alone induced adverse, inhibitory effects on spermatogenesis and serum testosterone, did not influence serum FSH and LH but increased 14-fold the level of prolactin. Except from testosterone, EB given with hFSH not only overcame inhibitions, but multiplied hFSH stimulatory effects on spermatogenesis up to 30-times of control values. In addition, after FSH+EB premeiotic germ cell ratio reached adult type value precociously. Estradiol may play regulatory roles in testicular maturation (1) inhibitory, direct one or resulting from decrease in testosterone secretion; (2) stimulatory, by enhancement of FSH action, with a possible involvement of prolactin that may act in concert with FSH.

Animals↗
PubMed1978

Androgen and estrogen formation in women with ovarian hyperthecosis.

Women with ovarian hyperthecosis were studied and found to have a plasma testosterone production rate of 2.1 mg/day, a value eight times greater than that of nonhirsute, ovulatory women. The severity of hirsutism and virilization in these women was more closely correlated with the amount of testosterone produced than with plasma testosterone concentrations. The mean plasma production rates of androstenedione in these women, 8.6 mg/day, was more than three times that found in young women with no evidence of androgen excess. There was a marked gradient between ovarian and peripheral venous plasma concentrations for both C19 steroids. Following ovarian wedge resection or oophorectomy, there was a precipitous fall in the peripheral venous concentrations of these steroids. These observations support the view that the major source of excess androstenedione and testosterone secretion in these subjects was the ovaries. The rate of estrone formation in these women, 106-345 microgram/day, was the result of extraglandular aromatization of plasma androstenedione.

Adolescent↗
PubMed1996

Time- and dose-dependent antigonadotropic activity of oxidation products of gallic acid and pyrogallol on Leydig cells in vitro.

Auto-oxidation products of plant phenolics in alkaline medium, such as gallic acid and pyrogallol were used to show antigonadotropic activity. The complex mixture of oxidation products was extracted from aqueous medium successively by ethyl ether and ethyl acetate. The fractions obtained were tested on a model of mouse Leydig cells in vitro. All compounds used inhibited luteinizing hormone-stimulated testosterone secretion during 6 and 24 h culture whereas basal secretion was stimulated by pyrogallol oxidation products. Not only low molecular weight substances extracted by organic solvents but also the remaining water soluble, dark brown, high molecular weight products were found to be antigonadotropically active.

Animals↗
PubMed1995

Spontaneous follicular and luteal function in infertile women with oligomenorrhoea: role of luteinizing hormone.

OBJECTIVE: There is a paucity of longitudinal endocrine studies of infertile patients with oligomenorrhoea. We have assessed the frequency and quality of spontaneous follicular development and luteal function in patients with oligomenorrhoea and infertility (PCOS), and have related the observed criteria to circulating LH activity. DESIGN: Prospective detailed investigations in a cohort of unselected patients. PATIENTS: Infertile women with oligomenorrhoea (PCOS, n = 131) presenting to the infertility clinic at the Royal Infirmary, Glasgow. MEASUREMENTS: Patients were monitored with frequent plasma oestradiol (E2) concentration assessments over a minimum period of 3 weeks, starting more than 2 weeks after a menstrual bleed. When follicular maturation was identified the patient provided daily blood samples through to her ensuing menstrual bleed, and E2, progesterone, total testosterone, FSH and LH were assessed in these samples. Luteal phase progesterone profiles were assessed between the days LH surge +2 and LH surge +6 by means of a progesterone index. RESULTS: Forty-eight per cent of the patients showed evidence of follicular development. The oestradiol profiles in the patients showing follicular growth were normal, but the progesterone curve was sub-normal in the early luteal phase, due to a high proportion of deficient luteal phases. The mean LH concentrations were elevated in the whole group, but no difference was observed between the mean LH values for those patients showing spontaneous follicular development and those who did not, and the incidence of ovulation was similar in the normal LH and elevated LH groups. Similarly, no relation was established between LH and the quantitative assessment of luteal phase progesterone profiles (progesterone index), and the distribution of progesterone indices was similar in the normal LH and elevated LH groups. Testosterone concentrations were positively correlated with LH (p = 0.008) but not with the incidence of spontaneous follicular growth. There was no significant difference in the incidence of spontaneous ovulation between the patients with elevated or normal mean follicular phase testosterone concentrations. CONCLUSION: The data indicate that both LH and testosterone secretion in PCOS were closely linked, but that neither was directly linked to the incidence or inhibition of spontaneous follicular development in PCOS, or to the disturbance in luteal phase progesterone profiles.

Adult↗
PubMed2000

The effect of callosotomy on testicular steroidogenesis in hemiorchidectomized rats: a pituitary-independent regulatory mechanism.

In recent years, increasing number of data indicate that cerebral structures exert a direct, pituitary-independent, neural regulatory action on the endocrine glands. In addition, both experimental and clinical observations indicate functional asymmetry of the control system. Therefore, the objective of the present study was to study the effect of callosotomy on testicular steroidogenesis and serum gonadotrop concentrations in rats subjected to left- or right-sided orchidectomy. In animals underwent callosotomy plus left-sided orchidectomy the basal testosterone secretion in vitro of the remaining (right) testis was significantly higher than that of intact controls, and of rats subjected to sham surgery plus left orchidectomy. In contrast, either sham operation or callosotomy plus right-sided orchidectomy did not interfere with testicular steroidogenesis. Sham surgery or callosotomy plus left orchidectomy induced a significant rise in serum follicle-stimulating hormone concentration while right orchidectomy combined either with sham surgery or callosotomy did not alter this parameter. There was no statistically significant difference between experimental groups in serum testosterone and luteinizing hormone concentrations. The results indicate the involvement of the corpus callosum in a pituitary-independent neural control of testicular steroidogenesis. The data further suggest a different response in steroidogenesis of the left and the right testis following hemicastration and callosotomy.

Animals↗