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PubMed1996

[Testosterone-producing adrenal carcinoma: report of 2 cases].

We report two women aged 48 and 65 years old with hirsutism and a painful abdominal mass. Laboratory assessment showed serum testosterone levels of 500 and 321 ng/dl (normal values below 110 ng/ml). Abdominal CAT scans showed an adrenal mass in both patients. The younger woman was subjected to a surgical resection, the tumor relapsed two years later and the patient died. The other woman died during the first hospitalization. Adrenal tumors infrequently secrete testosterone as described in these two patients.

Adrenal Gland Neoplasms↗
PubMed2002

Effects of melatonin on Leydig cells in pinealectomized rat: an immunohistochemical study.

We have investigated immunohistochemically the effects of melatonin on Leydig cells in rat. Three groups of Wistar rats were used. Rats in group I and II were sham-pinealectomized (control) and pinealectomized, respectively, whereas rats in group III were pinealectomized and injected daily with melatonin for 2 months. At the end of the experiment, all animals were killed by decapitation and blood samples were obtained. Serum testosterone levels were determined with the use of a chemiluminescent enzyme immunoassay. Testicular tissue was collected and processed for semiquantitative evaluation of immunohistochemical testosterone staining. Intensity of immunostaining was determined on a scale between 0 (no staining) and 5 (heavy staining). In pinealectomized rats, serum testosterone levels were significantly increased as compared to sham-pinealectomized rats. Daily administration of melatonin after pinealectomy resulted in significant decreased serum testosterone levels as compared to levels in control and pinealectomized rats. Immunostaining of testosterone was moderate (3+) in sham-pinealectomized rats, heavy (5+) in pinealectomized rats and low (1+) in pinealectomized rats that were treated with melatonin, respectively. The results of our study indicate that pinealectomy induces increased testosterone secretion in Leydig cells and this increased secretion can be prevented by administration of melatonin.

Animals↗
PubMed1989

[Effect of immobilization stress on the gonadotropic function of the hypophysis in male hamadryas baboons (Papio hamadryas)].

The plasma levels of luteinizing hormone (LH) and testosterone were studied in intact and castrated male baboons exposed to 2- and 10-hour periods of immobilization. Presented data have shown that immobilization stress induced a marked decrease in LH concentration both in intact and castrated monkeys. Changes in LH concentration positively correlated with plasma levels of testosterone only during the experimental procedures. During three days after immobilization there was a sharp dissociation in the dynamics of testosterone levels remained low and LH returned to normal values. We can suggest that it is not absolute LH level that is responsible for the changes in testosterone secretion during the immobilization stress.

Animals↗
PubMedDate not supplied

The pattern of LH release in the adult ram influences the testicular steroidogenic response to individual LH pulses and is regulated by testosterone negative feedback.

Two experiments were conducted with adult intact rams (approximately 58 kg in body weight) in the nonbreeding season to investigate interrelationships between LH and testosterone secretion. In Experiment 1, LH pulse frequency was increased from approximately two to six peaks per 8 hours (for 56 hours) by injecting (iv) 10 micrograms NIH-LH-S18 every 80 minutes. Induction of a breeding season peak frequency produced a progressive 3-fold increase (P less than 0.01) in mean serum testosterone levels to values during the last 8 hours of treatment (12.6 +/- 1.2 ng/ml) that were 50% of those in the fall. In response to LH pulsing, testosterone peak amplitude increased (P less than 0.05) from 3.5 +/- 0.8 ng/ml to 6.7 +/- 0.7 ng/ml. In Experiment 2, the mean testosterone level was increased to breeding season values (for 96 hours) by injecting (im) 5 mg testosterone every 4 hours. Mean LH levels and LH peak frequency were decreased (approximately 70%, P less than 0.01) following 36 hours of treatment, and the LH response to exogenous GnRH was decreased (approximately 45%, P less than 0.01) by the final 4 hours Results indicate that for rams in the nonbreeding season, the testicular steroidogenic response to individual LH pulses is enhanced when pulse frequency is increased. When blood testosterone is elevated to breeding season levels, LH pulse frequency is severely impaired, while pituitary responsiveness to GnRH is diminished, as in the fall.

Animals↗
PubMed1988

Endocrine effects of oestrogen withdrawal in long-term treated patients with prostatic adenocarcinoma.

Eighteen patients with prostatic adenocarcinoma, treated with oestrogen for 45 months or more, were followed-up after withdrawal of oestrogen treatment. Serum concentrations of testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), oestradiol-17 beta, testosterone-oestradiol-binding globulin (TeBg) and prolactin were measured at different intervals between 3 and 42 months after cessation of treatment. Serum testosterone concentrations after cessation of oestrogen treatment were low (range 71.4 +/- 6.3 to 120.8 +/- 23.7 nmol/100ml), whereas the concentrations of LH (range 21.8 +/- 3.6 to 32.6 +/- 9.1 U/1) and FSH (range 31.2 +/- 5.5 to 54.7 +/- 9.5 U/1) were within or higher than the reference range. Prolactin (range 6.0 +/- 85.3 to 7.9 +/- 68.2 micrograms/1) was within the reference range. No significant changes in serum concentrations of testosterone, LH, FSH and prolactin occurred during the follow-up period. The serum concentrations of both oestradiol-17 beta and TeBg, found between 13 and 36 months after oestrogen cessation (range 43.8 +/- 4.6 to 46.2 +/- 5.9 and 64.0 +/- 2.5 to 86.0 +/- 10.0, respectively) were significantly lower than the concentrations found between 3 and 12 months (range 71.9 +/- 10.4 to 99.8 +/- 12.9 and 124.1 +/- 15.5 to 140.2 +/- 13.7, respectively). It is concluded that in patients with prostatic adenocarcinoma, long-term oestrogen treatment causes an irreversible impairment of Leydig cell function and consequently a reduced testosterone secretion after cessation of oestrogen treatment.

Adenocarcinoma↗
PubMed1983

Studies on seminiferous tubule fluid production in the adult rat: effect of hypophysectomy and treatment with FSH, LH and testosterone.

Seminiferous tubule fluid production in adult rats was studied using the technique of unilateral efferent duct ligation (EDL), the production rate representing the difference in testis weight over the time since ligation. Following EDL, fluid production increases linearly for 6 h and linearly at a slightly slower rate for a further 18 h with a sharp decrease thereafter. No differences in fluid production were noted for rats aged between 90-310 days. Forty-eight hours after hypophysectomy there was a significant fall (26%) in fluid production prior to any significant decrease in testis weight. Fluid production continued to decline with time after hypophysectomy eventually reaching a plateau 16-44 days later at levels approximately 15% of those found in control rats. Treatment of rats hypophysectomized 4 days earlier with ovine FSH for 3 days did not restore fluid production, but treatment with ovine LH, testosterone propionate (TP) or FSH together with TP for a similar duration all restored fluid production to normal. On the other hand, treatment of intact adult rats with ovine LH significantly increased fluid production but the effect of treatment with testosterone alone did not reach significance. The results indicate that in the adult rat, seminiferous tubule fluid production is controlled principally by testosterone secreted by the Leydig cell in response to LH stimulation.

Animals↗
PubMed2000

Role of the serotoninergic system in the acceleration of sexual maturation in wild Norway rats selected for reduced aggressiveness toward humans.

The role of the serotoninergic system in acceleration of the sexual development of domesticated rats (Rattus norvegicus) was assessed. The onset of age-related changes in hypothalamic serotonin during prepubertal period occurred earlier in domesticated than in aggressive male rats. Blockade of the serotoninergic system after p-chlorophenylalanine (PCPA) administration on days 40 and 44 delayed the development of the reproductive system in both aggressive and domesticated males. In 60-day-old rats treated with PCPA, levels of testosterone in plasma and the number of mature spermatozoa in epididymis were decreased compared to controls. At the same time, the administration of PCPA on days 30 and 34 did not modify basal testosterone secretion and other parameters in 60-day-old aggressive rats and produced a decrease similar to PCPA injections on days 40 and 44, although less pronounced, in the weights of testes in domesticated animals. Administration of 5-hydroxytryptophan (5-HTP), a precursor of serotonin synthesis, on days 30, 32, 34, 36 and 38 increased plasma testosterone levels and weights of the sex organs in 60-day-old domesticated males, but did not significantly affect the development of reproductive system in aggressive animals. These data indicate that serotonin stimulates sexual development of males during prepubertal period and this activating effect of serotonin occurs earlier in domesticated than in aggressive males. They also suggest that the acceleration in sexual maturation of domesticated rats could result from changes in the ontogenetic dynamic of hypothalamic serotonin induced by a selection for low aggressiveness towards man.

5-Hydroxytryptophan↗
PubMed1987

The response of the anterior pituitary and testes to synthetic luteinizing hormone-releasing hormone (LHRH) and the effect of castration on pituitary responsiveness in the maturing chicken fed aflatoxin.

The responsiveness of the anterior pituitary to exogenous luteinizing hormone-releasing hormone (LHRH; 20 micrograms/kg body weight) and the subsequent stimulation of testosterone secretion by the testes was studied after administration of dietary aflatoxin (10 ppm) to 9-wk-old male chickens. In both control and aflatoxin-treated males, there were significant (p less than 0.05) increases in plasma luteinizing hormone (LH) concentrations following LHRH administration, which peaked at 5 min post injection and declined thereafter. Plasma testosterone levels increased soon after the LHRH injection in control males, secondary to elevated LH levels in the peripheral circulation, and continued to increase throughout the experimental period. In contrast, this LH-induced elevation in plasma testosterone was delayed in aflatoxin-treated males, with no substantial increase until 20 min post-LHRH injection. In a subsequent experiment, castration of aflatoxin-fed males resulted in an altered response to exogenous LHRH, as compared to their intact counterparts. Based on these data, it appeared that while the LH-secretory capacity of the anterior pituitary was not diminished in birds receiving aflatoxin, the testicular response to exogenous LHRH was altered during aflatoxicosis. Additionally, the effect of castration on plasma LH profiles after LHRH administration provides preliminary evidence for extra-testicular effects of dietary aflatoxin on reproduction in the avian male.

Aflatoxins↗
PubMedDate not supplied

Mechanisms in the production of prepuberal reproductive defects in neonatal estrogenized male rats.

Neonatal estrogenization induced in prepubertal males atrophy of the testis and ventral prostate and increased the weight of the seminal vesicles. Atrophy of the testis was probably due to the inhibition of FSH and LH secretion: males estrogenized on day one and sacrificed daily from day six to day fifteen showed lower gonadotropin levels than their respective controls. In addition, daily FSH and LH administration (80 micrograms/100 g BW and 40 micrograms/100 g BW respectively) from day one to day fifteen increased testicular development more effectively in estrogenized than in control males and the differences between the two groups disappeared. Prostate atrophy was due to the decreased testosterone secretion. The reason for the hypertrophy of the seminal vesicles remains unclear: reduction in Prolactin levels due to bromocriptine treatment did not normalize the seminal vesicles weight, indicating that hyperprolactinemia was not the cause. Male rats estrogenized on day one, orchidectomized on day 5 and decapitated on day fifteen also showed hypertrophy in their seminal vesicles. These results indicate that testicular factors, other than testosterone, were not responsible for the vesicular hypertrophy. It seem possible that estrogens might act directly on vesicular growth.

Adrenal Glands↗
PubMed1975

Serum testosterone determination by mass fragmentography.

A mass fragmentographic reference method for the determination of plasma or serum testosterone is described. A fixed amount of [4--14C]testosterone (usually 10 ng) is added to a fixed amount of serum (usually 1 ml) and extracted with ether. The ether extract is purified by means of thin-layer chromatography. The purified testosterone is converted into the di-trimethylsilyl derivative by treatment with trimethylsilylimidazole. The amount of unlabeled testosterone is determined from the ratio between the recordings at m/e 432 and 434, obtained after analysis with a combined gas chromatograph-mass spectrometer equipped with a MID-unit (multiple ion detector). The two ions used correspond to the molecular peak in the mass spectrum of unlabeled and 4--14C-labeled testosterone, respectively. The relative standard deviation of the method was about 2.7 percent. The method was compared with a radioimmunoassay technique. There was a good correlation and the regression coefficient was about 0.83. A diurnal rhythm in testosterone secretion was confirmed both with the mass fragmentographic technique and with radioimmunoassay.

Adult↗
PubMed1983

Inhibitory effect of a new opioid agonist on reproductive endocrine activity in rats of both sexes.

Morphine and other opioid compounds such as the new benzomorphan derivative, bremazocine, inhibit the secretion of luteinizing hormone in rats of both sexes (1, 2, 3, 4). The aim of our work was to compare in rats the LH-secretion inhibiting properties of bremazocine, a putative opiate kappa agonist (5), with those of the mu agonist morphine. Acute administration of bremazocine (0.005 - 1 mg/kg s.c.) or of morphine (10 - 20 mg/kg s.c.) diminished serum LH levels and spontaneous ovulation in female rats in a dose-dependent manner. Chronic treatment with bremazocine significantly diminished LH and testosterone secretions in male rats which in turn led to a fall in weight of the prostate gland; prolactin and FSH secretions were not influenced significantly. The mu-antagonist naloxone, which increases LH release in rats, in acute experiments significantly antagonized the inhibiting effect of morphine, but not that of bremazocine on LH secretion. Neither the basal nor the LHRH-stimulated secretion of LH in pituitary cell cultures were changed by bremazocine (10(-11) to 10(-5) M), however the release of LHRH-like activity from hypothalamic fragments was significantly impaired by 10(-7) M bremazocine. In conclusion, the data presented here show that bremazocine is a new non-morphine-like opioid agonist which selectively inhibits LH release in rats.

Animals↗
PubMed1987

Decrease of mu opioid receptors in the brain and in the hypothalamus of the aged male rat.

Experiments have been designed in order to analyze whether the binding capability of mu opioid receptors in the brain of the male rat is modified by age. In a first experiment, the number of receptors (Bmax) and the constant of affinity (Ka) for the mu ligand 3H-dihydromorphine (3H-DHM) have been measured in the whole brain of male rats of 2, 15 and 22 months of age. In a second experiment the Bmax and the Ka for 3H-DHM have been evaluated in the hypothalamus of male rats of 2 and 22 months of age. In this experiment it was also investigated whether the administration of exogenous testosterone modifies the number and/or the affinity of the hypothalamic mu receptors. Serum levels of LH, FSH, prolactin and testosterone have been measured by specific RIAs. The results obtained show that: serum testosterone levels are significantly decreased in aged rats, while serum LH and FSH show only a small decline; serum prolactin is higher in old than in young animals; the number of mu receptors in the whole brain of 15 and 22 month old animals and in the hypothalamus of 22 month old rats is significantly lower than in the same tissues of young animals; the administration to old animals of testosterone, in doses able to bring back towards normal serum levels of testosterone, induces a decrease of LH and FSH, but has no effect on serum prolactin titers. Testosterone administration does not modify the number of hypothalamic mu opioid receptors, indicating that the decline of brain mu receptors in old animals is not the consequence of the physiological decline of testosterone secretion; in no instance the Ka for the mu ligand is significantly affected.

Aging↗
PubMed1988

Iron deficiency: effect on plasma luteinizing hormone and testosterone levels in the adult male rat.

We studied four groups of animals, all of which received an iron-deficient diet for 6 wk followed by a 4-wk recovery period during which all groups received Fe supplements. Group 1 (n = 12) and group 2 (n = 10) were intact male rats; group 1 received a dietary Fe supplement whereas group 2 received no Fe supplement. Group 3 (n = 12) and group 4 (n = 12) were castrated male rats; group 3 received a dietary Fe supplement whereas group 4 received no supplement. Analysis of circulating hormone values revealed that after 6 wk of dietary treatment, neither LH nor testosterone levels were affected by the Fe-deficient diet in either the castrated or intact groups. These observations suggest that neither testosterone secretion per se nor its feedback control by LH is affected by short-term Fe deficiency.

Animals↗
PubMed1990

Differentiation of Leydig cell precursors in vitro: a role for androgen.

An enriched fraction of mesenchymal-like cells was isolated from the testes of 21 day old rats. Testosterone production (ng/10(6) cells.24 hours) by these cells when cultured in vitro was measured by radioimmunoassay of HPLC-purified extracts of culture medium. In the presence of LH + DHT there was a significant increase in testosterone secretion from 22 +/- 10 ng after day 1 of culture to 284 +/- 75 ng on day 3 (P less than 0.01). By contrast, LH or DHT alone were without significant effect. We conclude that LH alone is insufficient but that androgen and LH induce mesenchymal-like Leydig cell precursors from 21 day old rats to produce testosterone.

Animals↗
PubMed1988

Characterization of the effects of clomiphene citrate on reproductive physiology in male rats of various ages.

Clomiphene citrate (clomiphene) inhibits reproduction in male rats; however, stimulatory effects have been reported at low doses. Male rats were implanted at 60 (adult), 35 (peripubertal) or 10 (prepubertal) days of age with pellets that delivered 0, 0.05, 0.5 or 5.0 mg clomiphene.kg-1.day-1 and were sacrificed after 7 or 14 days of treatment. Testis weight was unaffected by clomiphene in adult and peripubertal rats, but was reduced by all doses in prepubertal rats. Seminal vesicle and prostate gland weights were decreased to varying degrees by clomiphene in all animals, except seminal vesicle weight in peripubertal rats. Serum LH and testosterone were decreased by most doses in all age groups, whereas pituitary LH was decreased in prepubertal rats only. Pituitary GnRH and testicular LH receptor concentrations were reduced in all treated animals. Serum and pituitary FSH were decreased in pre- and peripubertal rats, whereas testicular FSH receptor concentrations were unaffected by treatment. In summary, 1) reproductive function was compromised by clomiphene and many responses were age-dependent, 2) reductions in gonadotropins suggest that clomiphene decreased their synthesis and/or release, and 3) decreased serum LH and testicular LH receptor concentrations were coupled to reduced testosterone secretion.

Age Factors↗
PubMed1985

Pituitary-testicular axis abnormalities in immature male hypothyroid rats.

The pituitary-testicular disturbances which follow the onset of hypothyroidism were studied in immature male Wistar rats rendered hypothyroid by treatment with methimazole (MMI) given in drinking water, starting at 40 days of age. Half of the animals continued on MMI (MMI group) up to 140 days of age; the remaining rats were withdrawn MMI at 100 days and injected thereafter s.c. with 3 micrograms of T3 daily, during the last 40 days (MMI + T3 group). Ten rats were used as controls (C group). Hypothyroidism induced in immature animals significantly decreased serum T4, T3, LH, PRL, and testosterone levels, and also impaired the normal growth of body and sex accessory glands. T3 replacement therapy helped to normalize serum hormonal levels, but the body and sex accessory gland weights were not fully corrected. Hypothyroidism also reduced the [125I]LH/hCG binding sites of testicular homogenates. T3 replacement was not able to improve the binding; nonetheless, the hormone-receptor affinity constant remained unaltered among the groups. Leydig cell responsiveness to hCG stimulation in vitro (0-82 nM) showed impaired testosterone production in the MMI group (25% of that found in the C group) and also in the MMI + T3 group (80% of that found in the C group). These data demonstrate that induction of hypothyroidism in the immature male rat leads to alterations in serum LH, PRL and testosterone levels, and suggest that thyroid hormones have a modulating action on the testis as far as LH-mediated testosterone secretion is concerned.

Animals↗
PubMed1989

Modulation by sex steroids of brain opioid receptors: implications for the control of gonadotropins and prolactin secretion.

Several experiments have been performed in order to analyze whether physiological or experimental changes of the endocrine environment might modify the binding characteristics of brain mu and kappa opioid receptors in the brain of the female and male rat. (a) In a first series of experiments, it has been observed that in the whole brain of regularly cycling female rats the number of mu receptors shows variation during the different phases of the estrous cycle. In particular a significant increase of the number of mu receptors has been observed in the morning of proestrus and in the afternoon of estrus. (b) In a second series of experiments, it has been shown that the administration of estrogens brings about a significant increase in the number of mu receptors in the hippocampus and in the thalamus of ovariectomized rats, while the administration of a regime including estrogen and progesterone induces a significant decrease of the number of mu receptors in the hypothalamus and in the corpus striatum. These data seem to indicate that hypothalamic mu receptors may be involved in the positive but not in the negative feedback control of LH secretion. (c) In a third series of experiments, it has been found that the number of mu receptors in the whole brain of 15- and 22-month-old male rats and in the hypothalamus of 22-month-old male rats is significantly lower than in the same tissues of young animals; moreover, the administration to old animals of testosterone does not modify the number of hypothalamic mu opioid receptors, indicating that the decline of brain mu receptors in old animals is not the consequence of the physiological decline of testosterone secretion but probably represents an autonomous phenomenon. (d) In a fourth series of experiments, it was shown that, in young male rats, the concentration of kappa receptors is extremely variable in different regions of the brain. The highest concentrations have been found in the hypothalamus and in the striatum; also in the mesencephalon and in the amygdala kappa receptors are present in rather elevated quantities; lower concentrations have been found in the thalamus, the frontal poles, the hippocampus and in the anterior and posterior cerebral cortex. These experiments have shown in addition that the process of aging induces an increase of the number of kappa receptors in the amygdala and in the thalamus; no age-linked modifications were observed in the other structures examined.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗
PubMed1980

Clinical, cytogenetical, histological, immunological and hormonal studies in a case of true hermaphroditism.

A true hermaphrodite with ambiguous genitalia and 46XX karyotype was studied from 18 months of age to 17 years. At 13 years, he developed an ambiguous puberty, with marked bilateral gynaecomastia and public hair score three. A relatively high testosterone level (21 nmol/l), not increased by hCG stimulation, was associated with a high LH level (6 UI/l). In the venous blood of the right ovotestis, the steroid concentrations were in the adult male range, especially testosterone (1400 nmol/l). After removal of the right gonad, large fluctuations of oestradiol levels were observed (150-810 pmol/l). The testosterone secretion of the left ovotestis was low, concentrations begin 4.2 and 130 nmol/l in peripheral and gonadal blood respectively at 16 years. A significant LH surge was induced by oral ethinyl-oestradiol before removal of the left gonad. The 5 alpha-reductase activity was normal in pubic skin. In the left gonad the concentrations of cytosol receptors for testosterone and 5 alpha-dihydrotestosterone (DHT) were significant: 14.5 and 65.5 fmol/mg protein respectively. However the plasma DHT level was not increased by hCG. Finally, the presence of H-Y antigen was demonstrated on lymphocytes. This accords with the presence of testicular tissue in an XX subject, and with significant testosterone production. The high testosterone production did not prevent the appearance of a positive oestrogen-LH feedback. The relative peripheral insensitivity to testosterone, is, in some ways, inconsistent with the presence of receptors for androgens.

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