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PubMed1994

Cryopreservation of rat Leydig cells for in vitro and in vivo studies.

Leydig cells lose their ability to secrete testosterone following short-term in vitro culture. A procedure for effective storage of these cells would be useful. In this study, rat Leydig cells were cryopreserved in the presence of 10, 15 or 20% dimethylsulfoxide (DMSO) at approximately 1 degree C/min to -70 degrees C and then stored in LN2. After thawing, the cells cryopreserved in the presence of 15% DMSO showed the highest viability of over 75%. These cells secreted basal levels of testosterone in vitro as well as responded to hCG stimulation by secreting over 9-fold increase in testosterone. The viability of these cells was further confirmed by the demonstration of 3 beta-HSD positive cells under the kidney capsule of rats isografted with cryopreserved Leydig cells. This study demonstrated that purified rat Leydig cells can be cryopreserved and the cryopreserved cells retained normal function and were responsive to hCG stimulation. Cryopreservation is a simple procedure for long-term storage of functional Leydig cells.

3-Hydroxysteroid Dehydrogenases↗
PubMed1982

Plasma androgen levels after subcapsular orchiectomy or estrogen treatment for prostatic carcinoma.

In this study evolution of plasma androgen levels in patients with advanced prostatic carcinoma, treated by either subtotal bilateral orchiectomy or estrogens, was studied in order to determine whether subcapsular orchiectomy results in complete elimination of testicular testosterone secretion and whether in subsequent months there occurs any reactivation of eventually remaining Leydig or increased adrenal androgen secretion. This study, performed on 40 patients having undergone bilateral subcapsular orchiectomy for prostatic carcinoma, shows that this intervention results in testosterone levels in the female range and that during the year following subcapsular orchiectomy there is no evidence for reactivation of Leydig cells or for increased adrenal androgen secretion as evaluated from plasma testosterone, androstenedione, and dehydroepiandrosterone sulphate levels. In patients treated with estrogens we found no evidence for stimulation of adrenal androgen secretion, whereas in neither group of patients with prostatic carcinoma we found evidence for increased androgen levels at the time of recurrence of the carcinoma.

Androgens↗
PubMed1991

Hypogonadal impotence treated by transdermal testosterone.

The transdermal therapeutic system for testosterone (TTS-T) (ALZA Corp.), applied to the scrotal skin for twenty-two hours daily, was tested for twelve weeks on 4 men with hypogonadal impotence; 2 of these men wore TTS-T for as long as twenty-six months. The 40 cm2 system delivered a daily dose of 2.8 +/- 0.16 (S.E.) mg (nominal dose 2.4 mg) and the 60 cm2 system delivered a dose of 3.99 +/- 0.24 mg (nominal dose 3.6 mg). Both systems promptly increased serum testosterone and dihydrotestosterone (DHT) to physiologic levels, restoring normal erectile activity with an increased frequency of ejaculation and a positive effect on both mood and energy. There were no changes in serum sex binding globulin and estradiol, prostate or breast size, hematologic or liver function measures, or urinary flow and frequency. There were no significant changes in serum cholesterol or low-density lipoproteins, but high-density lipoproteins tended to decline slightly. There were no dermatologic problems associated with the system. The tenfold increase in DHT over baseline levels was attributed to 5-alpha reduction of testosterone in the scrotal skin. The TTS-T is convenient, reliable, and mimics normal physiologic testosterone secretion and levels more closely than conventional methods of testosterone replacement.

Administration, Cutaneous↗
PubMed1987

Differential effects of chronic testosterone treatment on the onset of puberty in male rats.

Immature male rats were daily injected with 5 or 10 micrograms testosterone propionate (TP)/100 g b.w. from day 5 after birth through day 30 or through the day at which spermatozoa appeared in preputial smears (SpA). The age and body weight at preputial separation (PS) and SpA as well as the testes weight on the day of SpA were recorded. Reduced testicular weights as compared to the controls injected with oil were found in all experimental groups. Whereas daily injections of 5 micrograms TP/100 g b.w. did not alter the age and body weight at PS and SpA, administration of the higher TP dose from day 5 through day 30 resulted in highly significant delay of PS and SpA. This effect was almost completely abolished if treatment was continued to the day of SpA. In otherwise untreated males, however, injections of 10 micrograms TP/100 g b.w. from day 30 through the day of SpA did not advance the spontaneous onset of puberty. The findings suggest that slight elevation of the circulating testosterone level during infancy causes impairment of testicular functions resulting in retardation of spermatogenesis and, presumedly, long-lasting reduction of testosterone secretion. The effect can be abolished by substitution of testosterone during the late prepubertal phase, but spontaneous sexual maturation can probably not be accelerated in this way.

Aging↗
PubMed2004

Relationship between serum testosterone and activities of testicular enzymes after continuous and intermittent training in male rats.

To gain more information on the effects of training types on testosterone secretion, the present study investigated the relationship between serum testosterone (ST) and the activities of oxydoreductive enzymes in Leydig cells to continuous and intermittent training regimes. Male rats swam with a load of 3.5 % body weight for 90 min in the continuous training group, and 15 min separated by a 7-min rest interval x 6 times in the intermittent training group, 6 days per week for 5 weeks. ST were measured immediately and 24 h after exercise, and the activities of SDH, LDH and G6PDH in Leydig cells were measured 24 h after exercise, following 5 weeks of training. It was found that ST declined following continuous (0.54 +/- 0.32 nmol/l) and intermittent (1.64 +/- 1.80 nmol/l) exercise compared to sedentary group (9.55 +/- 5.17 nmol/l). This diminishing effect on ST was still significant 24 h after continuous exercise (5.96 +/- 2.79 nmol/l), not after intermittent exercise (7.41 +/- 4.77 nmol/l). The activities of SDH and LDH increased, whereas G6PDH decreased in Leydig cells, after both continuous and intermittent training. SDH and G6PDH showed the high activities in the intermittent training group relative to continuous training group. These differences in the activities of SDH and G6PDH might be considered as the possible causes for ST responses to training types.

Animals↗
PubMed1987

Long-term suppression of a testosterone-producing ovarian tumour by oestrogen/progestogen therapy.

A 44-year-old lady presenting with hirsutism was found to have a testosterone-secreting Leydig cell tumour of the right ovary. Serum testosterone levels were adequately suppressed for 8 years by combined oestrogen/progestogen preparation (Microgynon 30, Schering, West Sussex). The fall in gonadotrophin and testosterone levels during therapy and their rise after stopping therapy suggests that the tumour was gonadotrophin dependent.

Adult↗
PubMed1988

Characterization of the regenerated Leydig cell population of the rat after destruction by ethylene-1,2-dimethanesulphonate.

The Leydig cells repopulating the adult rat testis after destruction by a single injection of the cytotoxic ethylene-1,2-dimethanesulphonate (EDS) were investigated. After 14 days, serum concentrations of LH and FSH were significantly raised and concentrations of testosterone in the serum and testis reduced. At 21 days, hormone concentrations had returned to within the normal range. Binding of 125I-labelled human chorionic gonadotrophin (hCG) to testis homogenate, however, was still less than 10% of normal. After 21 or 28 days the 125I-labelled hCG binding profiles of isolated Leydig cells from EDS-treated rats, separated on a Percoll gradient, showed a single peak similar to that of immature (25 days old) rats. After 49 days, 125I-labelled hCG binding resolved into two peaks more like that of normal adult rats. Using a quantitative cytochemical method, 3 beta-hydroxysteroid dehydrogenase activity in individual Leydig cells of unfixed testis sections was determined. Activity was increased by 70% (P less than 0.05) in repopulating Leydig cells 21 days after EDS treatment compared with cells from vehicle-treated rats. In addition, Leydig cells were still capable of further 'in-vivo' stimulation by pharmacological doses of hCG. These data indicate that Leydig cells repopulating the testis are homogeneous. Fewer cells from the newly formed population are capable of maintaining normal serum concentrations of testosterone and must thus be individually more active in secreting testosterone. In these respects, the Leydig cells repopulating the adult rat testis after EDS treatment more closely resemble those of the fetal rat testis.

3-Hydroxysteroid Dehydrogenases↗
PubMed2003

The challenges of testosterone deficiency. Uncovering the problem, evaluating the role of therapy.

In addition to its relatively uncommon congenital causes, testosterone deficiency in men occurs in a diverse range of clinical conditions. Even healthy men are now known to begin experiencing progressive yet subtle declines in testosterone secretion after age 30. Diagnosis can be challenging, and testosterone replacement therapy does not alleviate all symptoms in all men. Nevertheless, some men can get relief with intramuscular long-acting testosterone esters, transdermal testosterone patches, or transdermal testosterone gel.

Hormone Replacement Therapy↗
PubMed1975

Gonadotropin-induced proliferation of endoplasmic reticulum in an androgenic tumor and its relation to elevated plasma testosterone levels.

The development of gonadotropin-induced structural change in a testosterone-secreting Leydig cell tumor and its relationship to plasma testosterone levels were studied in castrate, tumor-bearing mice 2 hr after daily injections of human chorionic gonadotropin (HCG). Tumor cells from control animals were small, averaging less than 1.0 X 10(-9) ml in volume, and were poorly differentiated, having very little smooth endoplasmic reticulum (SER) in their cytoplasm. Average plasma testosterone levels in these mice were near 1.3 ng/ml. Although a five-fold rise in plasma testosterone was measured 2 hr after the first HCG injection, no changes in the endoplasmic reticulum were detected at this time. After the second injection, plasma testosterone rose to only twice control levels, while ultra-areas of mixed rough endoplasmic reticulum and SER. Modest amounts of SER had appeared in many tumor cells after the third injection, and plasma testosterone showed a six-fold rise. Between the third and fourth injections, cell volume increased by about 70% as large accumulations of SER appeared in the cytoplasm of most cells. Plasma testosterone again rose to five times control levels. Increased cell volume and abundant SER were maintained by continuing daily injections of HCG, while the 2-hr plasma testosterone response persisted at five to six times the control level. These findings show that a maximal elevation of plasma testosterone can occur prior to changes in the endoplasmic reticulum of Leydig tumor cells. However, they also suggest that daily repetition of the maximal functional response requires that the cells acquire large quantities of newly produced SER.

Animals↗
PubMed2002

Leuprorelin acetate in prostate cancer: a European update.

This review provides an update on leuprorelin acetate, the world's most widely prescribed depot luteinising hormone-releasing hormone analogue. Leuprorelin acetate has been in clinical use in the palliative treatment of prostate cancer for more than 20 years, but advances continue to be made in terms of convenience and flexibility of administration, and in the incorporation of leuprorelin acetate into novel treatment regimens. The drug is administered in the form of a depot injection containing leuprorelin acetate microspheres, and is at least as effective in suppressing testosterone secretion as orchiectomy. In patients with prostate cancer, serum testosterone levels are reduced to castrate levels (< or = 50 ng/dl) within 2-3 weeks of the first one-month depot injection of 3.75 mg or three-month depot injection of 11.25 mg. Both the one-month and three-month formulations are effective in delaying tumour progression and alleviating symptoms of locally advanced and metastatic prostate cancer. Tolerability is generally good, with side-effects reflecting effective testosterone suppression. Recent studies have investigated the place of leuprorelin acetate as part of continuous or intermittent maximal androgen blockade (MAB) and in neoadjuvant therapy (i.e. to reduce the size of the prostate and downsize the tumour before radiotherapy). Additional formulations and presentations are in development, including a six-month injection, with the aim of adding to the clinical flexibility and patient acceptability of this important palliative treatment for prostate cancer.

Antineoplastic Agents, Hormonal↗
PubMedDate not supplied

Comparison of cellular and secreted proteins of macrophages from the testis and peritoneum on two-dimensional polyacrylamide gels: evidence of tissue specific function.

It has been shown that the testis contains a population of cells with many characteristics typical of macrophages of other tissues. However, these macrophages are unique in that they secrete a product(s) that is responsible for stimulating testosterone secretion by Leydig cells while peritoneal macrophages have no similar effect. The purpose of the present study was to compare the pattern of cellular and secreted proteins of rat testicular macrophages to those of peritoneal macrophages using two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). Cellular and secreted proteins of cultured macrophages from the testis and peritoneum were labeled with 35S-methionine and 35S-cystine and then analyzed by 2D-PAGE using a computer-assisted image analysis system. It was found that the patterns of both cellular and secreted proteins of testicular macrophages were vastly different than those of peritoneal macrophages. One striking difference was the presence of a family of proteins in the 47 kd range, with a range of pI from 5.7-6.3 that represented approximately 57% of the total protein secreted by testicular macrophages. Proteins of similar molecular weight and pI represented only approximately 15% of the total peritoneal macrophage secreted proteins. Many other differences were observed in less abundant cellular and secreted proteins. These studies strongly support the concept that macrophages are functionally heterogeneous and secrete a group of proteins characteristic to the histological location of these cells.

Animals↗
PubMed1979

Changes in plasma oestradiol-17beta, progesterone, testosterone, LH and fertility after treatment with I.C.I. 80, 996.

Fifty heifers were twice injected with I.C.I. 80, 996 and inseminated 72 h and 96 h after the second administration. Twenty eight of them (56%) became pregnant. Changes in plasma oestradiol-17 beta, progesterone and LH concentrations around the oestrus following the second injection were similar to those occurring in spontaneous oestrus. The pattern of testosterone secretion resembled that of oestradiol;-17 beta. The highest testosterone concentration (135 +/- 24 pg/ml) was measured on the third day after treatment with I.C.I. 80, 996.

Animals↗
PubMed1978

Endocrine effects of alcohol.

A variety of effects of alcohol on endocrine function are now well documented. Clinically, the most important of these are alcohol-induced 'pseudo-Cushing's syndrome' and a syndrome of hypothalamic-pituitary-adrenocortical unresponsiveness, both of which result from long-term over-indulgence, and impairment of testosterone secretion which may occur following relatively short-term drinking. Evidence indicates that a number of different mechanisms are responsible for mediating the effects of alcohol on endocrine function. In a few instances (e.g. inhibition of vasopressin secretion and impairment of steroidogenesis resulting in a fall in testosterone production rate), alcohol appears to influence directly the release or synthesis of individual hormones. However, the majority of the endocrine effects of alcohol are probably indirect, resulting from either the stress of intoxication (stimulation of cortisol, catecholamines and possibly GH and prolactin), changes in the level of intermediary metabolites (e.g. a fall in circulating FFA stimulating GH secretion) or changes in the metabolism of hormones (e.g. catecholamines, oestrogens, androgens) resulting from alteration in intracellular redox state or tissue damage.

Adrenal Cortex↗
PubMed1993

Maintenance of sperm production in bucks during a third year of short photoperiodic cycles.

We have previously shown that reproductive seasonality of bucks was prevented for 2 consecutive years by short photoperiodic cycles. To determine the effect of the length of treatment time on bucks subjected to the same photoperiod conditions, experiments were continued for a third consecutive year on 3 groups of 6 Alpine and Saanen bucks. The control group was kept under natural photoperiodic conditions, while the experimental groups were exposed alternately to 1 month of long days and 1 month of short days (group 2M) or to 2 months of long days and 2 months of short days (group, 4M). Prolactin profiles indicated that bucks from both experimental groups responded adequately to rapid photoperiod changes as their plasma prolactin levels were significantly higher in long days (mean +/- SEM; 2M: 61.1 +/- 15.9 ng/ml; 4M: 102.2 +/- 13.5 ng/ml) than in short days (2M: 35.3 +/- 8.2 ng/ml; 4M: 46.1 +/- 9.0 ng/ml). Testosterone secretion was also dependent on day length (P < 0.0001), since testosterone concentrations of experimental animals were higher during long days (2M: 7.0 +/- 0.7 ng/ml; 4M: 10.2 +/- 1.1 ng/ml) than during short days (2M: 4.3 +/- 0.4 ng/ml; 4M: 5.0 +/- 0.9 ng/ml). Furthermore, controls displayed a high level of sexual behavior (always higher than 10%) and the proportion of bucks unable to ejaculate was significantly lower (P < 0.01) than the experimental animals (2M: 25.6%; 4M: 28.1%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1976

Prolactin and testosterone: independent circulating levels in hyperprolactinemic and normoprolactinemic amenorrhea. The effect of prolactin suppression by bromocriptine.

In order to elucidate the pituitary regulation of the female testosterone secretion, we studied by radioimmunoassay the circulating prolactin (PRL) and testosterone-dihydrotestosterone (T-dT) levels in 12 hyperprolactinemic and 12 normoprolactinemic patients with secondary amenorrhea. After the basal levels had been recorded, each patient was given bromocriptine for two weeks, 2.5 mg twice daily, and repeat estimations of the PRL and T-dT levels were done. We found no significant difference in the basal T-dT levels between normoprolactinemic and hyperprolactinemic patients, and no significant correlation between the PRL and T-dT levels in either group. Although the PRL levels of the hyperprolactinemic patients were greatly suppressed by bromocriptine, the T-dT levels showed no systematic change. In normoprolactinemic patients, the T-dT concentrations were somewhat lower during bromocriptine treatment, but the difference from basal levels was not statistically significant (0.05 less than P less than 0.1). Our results suggest that in patients with secondary amenorrhea PRL does not interfere directly with T-dT secretion, or vice versa.

Adult↗
PubMed1993

Effects of bromocriptine-induced hypoprolactinaemia on gonadotrophin secretion and testicular function in rams (Ovis aries) during two seasons.

The influence of low circulating concentrations of prolactin on gonadotrophin and testosterone secretion, sperm production and testicular growth was investigated in rams during two different seasons. Treatment of Dorset rams (n = 23) with bromocriptine (4 mg day-1) during the spring (n = 11) and autumn (n = 12) caused a significant decrease in basal, mean and total serum prolactin concentrations (P < 0.01). In spring, serum prolactin concentrations returned to pretreatment values, one week after the termination of treatment. Basal, mean and total serum concentrations of LH were significantly higher in treated rams than in controls during the treatment period in autumn (P < 0.05). Secretion of LH was not affected by bromocriptine treatment during spring. There were no differences in the secretion of FSH between treated and control rams in either season. Serum concentrations of testosterone were significantly lower in treated rams than in control rams during the treatment period in autumn (P < 0.05) but not during spring. Semen volume from treated rams was significantly lower during the period after treatment in autumn (P < 0.05). Scrotal circumference decreased during both seasons in treated animals, but this change in size was significant only during spring (P < 0.05). Conversely, there was an increase in scrotal circumference in control rams during both seasons. It is concluded that prolactin may (i) affect LH secretion and, (ii) influence testicular function in rams, by directly affecting testosterone and semen production during autumn, and retarding testicular growth in spring.

Animals↗
PubMed2001

Testosterone-producing adrenocortical neoplasm in a 6-year-old boy.

Adrenal tumours that predominantly secrete testosterone are virtually unknown in prepubertal male patients. We present the case of a 6-year-old boy with premature sexual development and markedly elevated serum testosterone, but normal urinary steroid levels. Diagnostic imaging demonstrated a spherical tumour of the left adrenal gland. Surgical excision led to normalisation of testosterone levels, and postoperative serial low hormone measurements ruled out tumour recurrence.Although extremely rare, this case illustrates that testosterone-producing adrenal adenomas may be encountered in boys without urinary steroid elevation. Surgical excision promises a definite cure. Testosterone is a useful tumour marker in these patients until the beginning of puberty.

Adrenal Cortex Neoplasms↗
PubMed1982

Hormonal interrelationships between hypothalamus, pituitary and testis of rams and bulls.

This mini-review aims to summarize some of our recent findings relating to testicular function and feedback control of the hypothalamic-pituitary axis by testicular steroids in rams and bulls. Testosterone secretion in intact males is not tonic, but is characterized by episodic pulses. This pattern of secretion is dictated by inputs of the central nervous system via secretions of the hypothalamus (luteinizing hormone-releasing hormone; LHRH) and anterior pituitary (luteinizing hormone; LH). A temporal relationship exists between concentrations of LH and testosterone in serum and evidence is presented that strongly suggests that their episodic secretion is dependent on discrete episodes of LHRH discharge from the hypothalamus. Based on data from experiments with rams and bulls, I suggest that acutely castrated males (but not chronic castrates) remain susceptible to the negative feedback effects of testosterone, i.e., LH concentrations remain suppressed in serum of animals given testosterone replacement therapy immediately following castration. Estradiol-17 beta, on the other hand, abolishes pulsatile LH release and suppresses mean LH concentrations in both acute and chronic castrates. Therefore, testosterone feedback on LH secretion may, in part, involve extragonadal conversion to estradiol-17 beta to block pulsatile LHRH release. The potent inhibitory effects of estradiol on LH secretion provide an experimental probe for future investigations relating to mechanisms controlling male reproduction.

Animals↗