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Testosterone, gonadotropin, and cortisol secretion in male patients with major depression.

OBJECTIVE: Previous studies of sex hormone concentrations in depression yielded inconsistent results. However, the activation of the hypothalamic-pituitary-adrenal system seen in depression may negatively affect gonadal function at every level of regulation. The objective of this study was to explore whether major depressive episodes are indeed associated with an alteration of gonadal function. METHODS: Testosterone, pulsatile LH secretion, FSH, and cortisol were assessed using frequent sampling during a 24-hour period in 15 male inpatients with major depression of moderate to high severity and in 22 healthy comparison subjects (age range 22-85 years). RESULTS: An analysis of covariance model showed that after adjustment for age only, daytime testosterone (p < .01), nighttime testosterone (p < .05), and 24-hour mean testosterone secretion (p < .01) were significantly lower in the depressed male inpatients. There was also a trend for a decreased LH pulse frequency in the depressed patients (p < .08). CONCLUSIONS: Gonadal function may be disturbed in men with a depressive episode of moderate to high severity.

Adult↗

Effect of cell purity, cell concentration, and incubation conditions on rat testis Leydig cell steroidogenesis.

This study examines the effects of cell purity and incubation conditions on testosterone production by rat testis Leydig cells in short-term primary culture. Both basal and luteinizing hormone (LH)-stimulated testosterone production were affected by the purity of the cell preparation, i.e., as the purity of the cell preparation was increased the amount of testosterone produced per Leydig cell was also found to increase. The stimulation ratio of testosterone production, calculated as the secretion of testosterone in the presence of LH (100 ng/ml) divided by the basal secretion of testosterone, increased with the increase in plating density (20,000 to 200,000 cells per well). This pattern of change was independent of the vessel and volume of incubation. In terms of the absolute amount of testosterone produced, increasing the plating density led to a decrease in the amount of steroid produced both basally and in response to LH. Composition of the incubation medium also had an effect on testosterone production; phenol red and sodium bicarbonate exerted negative effects. At all temperatures studied (4 degrees, 24 degrees, 34 degrees, and 37 degrees C), LH increased testosterone production and the degree of stimulation increased with temperature. We conclude that cell purity and incubation conditions markedly affect rat Leydig cell steroidogenesis in vitro. Furthermore, the manner in which the results are presented can affect their interpretation.

Animals↗

T3 directly stimulates basal and modulates LH induced testosterone and oestradiol production by rat Leydig cells in vitro.

The effect of T3 on basal and LH mediated synthesis and secretion of testosterone and oestradiol by puberal rat Leydig cells was studied in vitro. Percoll gradient purified Leydig cells (1 x 10(3)) were cultured for 48 hours at 34 degrees C in a medium containing a range of 5-400 ng/mL concentration of T3 or ovine LH after 24 hours initial culture at 37 degrees C. T3 increased testosterone and oestradiol secretions in a dose dependent manner which reached the saturation point with 50 ng dose. While the minimum effective dose of T3 (25 ng) potentiated the stimulatory effect of the minimum effective dose of LH (25 ng) on testosterone secretion, it suppressed the effect of the saturation dose of LH (100 ng). Fifty ng T3 quelled the stimulatory effect of either dose of LH. Both doses of T3 increased oestradiol secretion, irrespective of the dose of LH. Addition of androstenedione (500 ng/mL) to the culture medium enhanced 25 ng T3 induced testosterone and oestradiol secretions. While androstenedione potentiated the stimulatory effect of T3 (25 ng) on LH (25 ng) induced testosterone and oestradiol secretions, it reversed the inhibitory effect of 50 ng T3 on LH mediated testosterone secretion which was accompanied by a decrease in oestradiol secretion. Puromycin (35 microg/mL) suppressed the stimulatory effect of T3 on basal and LH mediated testosterone and oestradiol production. Taken together, the present results indicate a direct stimulatory effects of T3 on basal production of testosterone and oestradiol by Leydig cells and its modulatory effect on LH mediated steroidogenic activity varies depending upon the intensity of LH stimuli.

Androstenedione↗

Testosterone regulates the secretion of thyrotrophin-releasing hormone (TRH) and TRH precursor in the rat hypothalamic-pituitary axis.

Orchidectomy has been reported to decrease concentrations of thyrotrophin (TSH) in the circulation of male rats without affecting serum levels of thyroid hormones. To understand the mechanism underlying this observation, we have measured the effect of gonadal status on the in-vitro release of TSH-releasing hormone (TRH) by male rat hypothalamic fragments. Because hormone release rates can be affected by changes in the post-translational processing of the hormonal precursors, we have also studied the corresponding changes in the concentrations of TRH and TRH-Gly, a TRH precursor peptide in hypothalamus and pituitary, by radioimmunoassay. We observed a significant decline in the in-vitro release of TRH from incubated hypothalami 1 week after castration, which was quantitatively reversed by testosterone replacement. Concentrations of TRH and TRH-Gly in the posterior pituitary, on the other hand, which derive from neurones of hypothalamic origin, increased significantly with castration and were returned to the normal range by testosterone replacement. We conclude that the primary effect of testosterone is the stimulation of hypothalamic TRH release, resulting in the depletion of TRH and TRH precursors from TRH-containing neurones which project into the median eminence and posterior pituitary.

Animals↗

The temporal response of rat testes to hCG stimulation during sexual maturation.

Serum testosterone responses to a single sc injection of hCG (25 IU/100 g body weight) were monitored for 5 days in rats throughout sexual maturation (22-70 days). Two hours after hCG injection serum testosterone levels rose in 22, 37 and 53 day-old animals and remained elevated for 2 days, returning to control levels on day 3. This response differed markedly from the biphasic secretion of testosterone reported for adult animals. In 70 day-old animals the serum testosterone response approached that seen in adult animals. Testosterone levels were elevated 2 h after hCG injection (25.4 +/- 2.5 ng/ml) and declined significantly at 12 and 24 h to 17.1 +/- 1.0 and 16.1 +/- 3.4 ng/ml, respectively. Testosterone levels tended to increase again on days 2 and 3 (19.9 +/- 2.8 and 21.1 +/- 3.5 ng/ml, respectively) but the increase was not statistically significant. This response differed markedly to the biphasic secretion of testosterone reported for adult animals. In vitro patterns of basal and hCG-stimulated testosterone secretion by decapsulated testes following a single hCG injection also changed during sexual maturation. In 22 day-old animals the testes exhibited refractoriness to in vitro hCG stimulation at 12 h, but testes from 37 day old rats were refractory from 2 to 24 h. In vitro testosterone responses of testes from 53 and 70 day-old rats were similar to that reported for adult rats with a period of refractoriness from 12 h to 2 days. This study demonstrates that during sexual maturation in the rat alterations occur in the temporal patterns of testosterone secretion in vivo and in vitro following hCG stimulation.

Aging↗

Pattern of secretion of luteinizing hormone and testosterone in the sexually mature male turkey.

Whether luteinizing hormone (LH) and testosterone (T) are secreted in pulsatile patterns was determined in sexually mature male turkeys. Turkeys were chronically cannulated and serially bled for three 8-hr periods covering the 24-hr day (14L:10D, n = 7, series B), or for two 12-hr periods covering the 24-hr day (14L:10D, n = 4, series C). Pulses of both LH and T occurred during both the light and dark portions of the 24-hr day. A portion of the secretory episodes of T, where the baseline level of LH was relatively low, was associated with prior peaks of LH secretion. Secretory episodes of T also occurred, where baseline levels of LH and T were both relatively high, without detection of prior peaks of LH. No differences were found between the photophase and scotophase portions of the photoperiod for either LH or T concentration. It is concluded that T is secreted in a pulsatile pattern in sexually mature male turkeys. However, LH is secreted in a pulsatile pattern only when baseline levels of both LH and T are relatively low. Neither LH nor T secretion is entrained by the photoperiod. Corticosterone was measured in hourly samples, but no changes in concentration occurred in association with the photoperiod.

Animals↗

Assessment of testicular testosterone production and Leydig cell structure.

Advances in two techniques have made the problem of assessing the acute and/or chronic effects of toxic agents on Leydig cell structure and testosterone synthesis and secretion amenable to study. First, in vitro testicular perfusion has been perfected to a point where it closely resembles in situ testosterone secretion. Second, now it is possible to quantify the proportion of Leydig cell cytoplasm occupied by the cellular organelles which contain steroidogenic enzymes. Herein, we report that inhibition of Leydig cell steroidogenic enzymes is reflected by reduced testosterone secretion by in vitro perfused rat and rabbit testes. Moreover, the activity of specific steroidogenic reactions can be monitored by measuring the secretion of reaction substrate(s) and product(s) from in vitro perfused testes. Testosterone secretion by in vitro perfused testes from five species is highly and positively correlated with the volume density of smooth endoplasmic reticulum in Leydig cell cytoplasm. Exploitation of these findings will allow toxicologists to quantitatively assess the effect of toxicants on Leydig cell testosterone biosynthesis and secretion, to identify the specific steroidogenic enzymes affected, to assess whether the membranous environment of the steroidogenic enzymes is compromised, and perhaps even to predict the deleterious effect of a toxic agent on Leydig cell steroidogenic function from a stereological assessment of Leydig cell ultrastructure.

Aging↗

Acute modulation of the hypothalamic-pituitary axis by intravenous testosterone in normal women.

Intravenous testosterone was infused for 6 hours in 23 ovulatory women, divided into five groups according to dose, to assess the effects of testosterone on gonadotropin secretion. Serum testosterone increased from 0.24 +/- 0.08 to steady-state levels of 1.63 +/- 0.18 ng/ml in the lowest-dose group (1) and to 42.1 +/- 3.3 ng/ml in the highest-dose group (4). In another group (5), patients were pretreated with testolactone, which prevented the estradiol rise associated with testosterone infusion. All groups except group 1 exhibited significant reductions in the delta maximum responses of luteinizing hormone to gonadotropin-releasing hormone during testosterone infusion compared with pretreatment levels (p less than 0.01). This was also evident for the testolactone group (5). There were no observed changes in serum follicle-stimulating hormone. Luteinizing hormone pulse frequency was decreased (p less than 0.05) with testosterone concentrations of 27.2 +/- 0.77 and 42.1 +/- 3.3 ng/ml (groups 3 and 4), but only in the highest group (4) was there a decrease in pulse amplitude (p less than 0.05). No luteinizing hormone pulse changes were observed with lower concentrations of testosterone. Plasma immunoreactive gonadotropin-releasing hormone levels remained undetectable or low in some of the groups sampled. These data suggest that short-term infusions of testosterone inhibit hypothalamic-pituitary function of normal women when high doses are used, and this effect may be independent of aromatization to estrogen.

Adult↗

The influence of feed restriction and subsequent re-feeding on gonadotrophin secretion and serum testosterone levels in male rats.

Male rats at 3 months were fully fed or were restricted to 50% of normal feed intake for 10 or 20 days. Underfeeding for either period resulted in reduced (P less than 0-05) body weight and pituitary weight but did not affect testicular weight. Underfeeding for 20 days resulted in reduced (P less than 0-05) weights of the seminal vesicles and ventral prostate. The serum concentration of LH was depressed (P less than 0-05) after 10 days of underfeeding and the pituitary concentration of LH was elevated (P less than 0-05) after 20 days of underfeeding. Neither serum nor pituitary concentration of FSH was influenced by feed level. Serum testosterone concentration was reduced in rats underfed for 20 days. In a second study, 2-month-old males were fully fed, underfed (15 days) or underfed and then re-fed (full feed) for 1, 2, 3 or 7 days. Underfeeding produced effects similar to those noted in the first experiment. Re-feeding of underfed rats resulted in body and ventral prostate weights returning to levels similar to those of fully fed controls by Day 7. The serum level of FSH was elevated (P less than 0-05) above the control level on Days 1, 3 and 7 of re-feeding, while the serum level of LH appeared to return to the control level. Serum testosterone level rebounded and exceeded (P less than 0-05) the control level on Days 1 and 2 of re-feeding.

Animals↗

Effects of Trypanosoma congolense infection in rams on the pulsatile secretion of LH and testosterone and responses to injection of GnRH.

Changes in pulsatile secretion of LH and testosterone and responses to exogenous GnRH were assessed at different stages of Trypanosoma congolense infection in rams. Jugular blood samples were collected every 15 min for 6 h followed by immediate injection of GnRH (20 micrograms i.v.) and further sample collection after 10, 20, 40, 60, 80, 100 and 120 min. This sampling and injection regimen was performed 5 days before infection (day -5) and 23 and 52 days after infection. T. congolense infection increased (P < 0.05) the mean plasma LH concentration over 6 h on day 23 (3.2 +/- 0.2 ng ml-1) and decreased (P < 0.05) the mean LH concentration on day 52 (1.2 +/- 0.2 ng ml-1, P < 0.05) compared with day -5 values (2.0 +/- 0.2 ng ml-1). Trypanosome infection induced a rapid decline in plasma testosterone concentration from a mean of 7.5 +/- 1.4 nmol l-1 on day -5 over 6 h to 3.6 +/- 0.4 nmol l-1 (P < 0.05) on day 23 and 1.7 +/- 0.3 nmol l-1 (P < 0.001) on day 52. The observed decline in plasma LH concentration in infected rams was not associated with reduced sensitivity of the pituitary to GnRH or its ability to release LH, as the LH response to exogenous GnRH was not impaired throughout the period of infection. However, the testosterone response to GnRH-induced LH stimulation was depressed on both days 23 and 52 after infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of passive immunization against testosterone on reproductive hormone secretion and ovarian function in dairy cows and pubertal beef heifers.

Multiparous dairy cows were divided in 3 groups from Day 5 up to Day 56 post partum: high energy level (Group H, n=10), low energy level (Group L, n=10) and low energy level plus anti-testosterone bovine immunoglobulins (Group LI, n= 10). Undernutrition decreased body weight, body condition score, milk yield and energy balance in Groups L and LI compared to Group H (P<0.05), but had no effect on secretory pattern of LH. Passive immunization against testosterone increased LH secretion in Group LI (P<0.05). Follicular score and the presence of follicles >/= 10mm on the ovary were not affected by underfeeding but were higher in Group LI than in Group L after immunization (P<0.01). The duration of the first luteal phase was shorter in Group H than in Groups L and LI and maximum progesterone levels reached were higher in Group LI than in Group H (P<0.01). Reproductive performance was not depressed by underfeeding and immunization. In the pubertal beef heifers maintained in anestrus by undernutrition had very low LH secretion. After passive immunization against testosterone, the increase of LH pulses number became almost significant (P=0.07). Following injection of exogenous LH, the number of follicles >/= 9mm was higher in immunized (Group I, n=8) than in control heifers (Group C, n=7). Group I developed a dominant follicle sooner and of greater size than Group C. Passive immunization against testosterone increased LH secretion and follicular development.

Journal Article↗

In vivo and in vitro stimulatory effects of Cordyceps sinensis on testosterone production in mouse Leydig cells.

The in vivo and in vitro effects of Cordyceps sinensis (CS) and its extracted fractions on the secretion of testosterone in mice were studied. CS, F2 (water soluble protein), and F3 (poorly water soluble polysaccharide and protein) significantly stimulated in vitro testosterone production in purified mouse Leydig cells. However, F1 (water soluble polysaccharide) had no effect (p>0.05). F2 and F3 stimulated in vitro testosterone production in dose- and time-dependent relationships with maximal responses at 3 mg/ml for 3 h (p<0.05). An in vivo study illustrated that testosterone levels in plasma were significantly increased by CS, F2, and F3, respectively (p<0.05). Because CS, F2, and F3 stimulated both in vitro and in vivo testosterone secretions in mice, it is possible that CS might contribute to an alternative medicine for the treatment of some reproductive problems caused by insufficient testosterone levels in human males.

Animals↗

Hormone secretion by euthyroid and hypothyroid rat ovaries during the early stages of hCG-induced ovarian cyst development.

This study was undertaken to examine ovarian steroid production during the early stages of hCG-induced ovarian cyst formation in the hypothyroid rat. Rats were placed into two groups with one group made hypothyroid by adding thiouracil to their diet. After 10 days, each group was divided into two subgroups with one subgroup receiving daily injections of hCG for 2 days and the other subgroup receiving saline. On the morning of Day 13, ovaries were removed and incubated for 2 hr. No significant difference in progesterone secretion was observed. However, ovaries from hypothyroid, hCG-treated rats secreted significantly more testosterone and estradiol than ovaries from vehicle-treated, hypothyroid rats and euthyroid, hCG-treated rats. In a second experiment, ovaries from euthyroid and hypothyroid rats treated with hCG were incubated in medium supplemented with 100 nM androstenedione and 0 or 100 ng FSH/ml. FSH failed to affect progesterone, testosterone, and estradiol secretions by ovaries from euthyroid, hCG-treated rats. In contrast, FSH significantly enhanced testosterone and estradiol secretion by ovaries from hypothyroid, hCG-treated rats. These results support the hypothesis that increased levels of testosterone and estradiol secretion have a central role in the induction of polycystic ovaries by hCG in the hypothyroid rat.

Androstenedione↗

Effect of thymectomy on serum gonadotrophins and testosterone concentration.

There is controversy about the relationship between thymic secretion and secretion of gonadotrophins and testosterone. One group of scientists reported that thymus is stimulatory to gonadotrophins and testosterone secretion, and according to other group thymic secretion is inhibitory to gonadotrophins and testosterone secretion. So we tried to observe what exactly happens to serum gonadotrophins and testosterone level following thymectomy. Thymectomy was performed in prepubertal animals and after 45 days of their operation serum gonadotrophins were measured by ELISA technique and serum testosterone was measured by RIA technique. The present study reveals a significant fall in serum FSH level along with significant rise in serum LH and testosterone level in male albino rats following thymectomy in comparison to that of sham thymectomized rats. It appears that thymus has an inhibitory influence on LH secreting gonadotrophs which has been withdrawn following thymectomy and as a result there occurs an increase in serum LH level. This LH stimulates interstitial cells of leydig and cause thereby an increase in serum testosterone level. The result also gives an indication that among the gonadotrophs in pituitary, one type is concerned with the secretion of LH while some gonadotrophs are concerned with secretion of FSH only; and the thymus possibly maintains the FSH secreting gonadotrophs intact at least till the age of puberty. Thymectomy may cause some disorganization of FSH secreting gonadotrophs which results in the fall in serum FSH level in thymectomized animals in comparison to that of sham thymectomized animal group.

Animals↗

Oestrogen and testosterone effects on hormone secretion and cell morphology of human pituitary tumours.

Estradurin (a polymer of 17-beta-oestradiol) has an inhibitory effect on the synthesis/secretion of PRL. This effect is assumed to be caused by the strong inhibitory effect of the drug on phosphatases. With increasing time of low doses of Estradurin (0.001 micrograms/ml) in vitro, the inhibitory effect on PRL secretion was overcome and the synthesis/secretion of PRL increased. The secretion of GH was unaffected in all concentrations (0.001-0.1 micrograms/ml) except 1 microgram/ml. A stimulatory effect of 17-beta-oestradiol (0.01 micrograms/ml) on the synthesis/secretion of PRL was suggested by the tissue from one post-pregnancy pituitary. Short time organ cultures from prolactinomas or tumors with a concomitant secretion of GH and PRL show no changes of GH or PRL secretion following incubation with (0.001-0.1 micrograms/ml) of 17-beta-oestradiol. However, electron microscopy of 17-beta-oestradiol incubated specimens revealed an increased number of lysosomes and inclusion bodies in the cell cytoplasm. Incubation with testosterone (0.001-1 microgram/ml) cause inhibition of PRL synthesis/secretion in two of three prolactinomas. In GH secreting tumours testosterone did not effect PRL or GH secretion in vitro when compared with controls. The ultrastructural analysis of specimens in which a decrease of PRL synthesis/secretion had occurred showed myelin figures in the cell cytoplasm and accumulations of amorphous electron dense inclusion bodies.

Adult↗