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PubMed1992

Decreased luteinizing hormone-stimulated progesterone secretion by preovulatory follicles isolated from cyclic rats treated with the progesterone antagonist RU486.

Since administration of the antiprogesterone RU486 to cyclic female rats at metestrus and diestrus results in increased serum levels of LH, estradiol, and testosterone at proestrus, we investigated whether RU486 affects follicular steroidogenesis. Female rats with a 4-day estrous cycle, induced experimentally by a single injection of bromocriptine on the morning of estrus, were given RU486 (2 mg) twice daily (0900 and 1700 h) on metestrus and diestrus. At proestrus the preovulatory follicles were isolated and incubated for 4 h in the absence and presence of LH. In the absence of LH, accumulation of estradiol, testosterone, and progesterone in the medium was not different for RU486-treated rats and oil-treated controls. In contrast, LH-stimulated estradiol, testosterone, and progesterone secretions were significantly lower in RU486-treated rats compared with controls. Addition of pregnenolone to the incubation medium resulted in a significantly lower increase of progesterone in follicles from RU486-treated rats compared with those from oil-treated controls. This suggests that 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) activity is decreased by administration of RU486 in vivo. Aromatase and 17 alpha-hydroxylase/C17-20 lyase activities were not affected: addition of substrate (androstenedione and progesterone respectively) did not affect differently the amount of product formed (estradiol and testosterone) in RU486- and oil-treated rats. However, LH-stimulated pregnenolone secretion was lower in follicles from RU486-treated rats compared with follicles from oil-treated controls, suggesting that either cholesterol side-chain cleavage activity or LH responsiveness is decreased. At proestrus the preovulatory follicles from RU486- and oil-treated rats were not morphologically different.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxysteroid Dehydrogenases↗
PubMed1994

Luteinizing hormone secretion and hypoandrogenaemia in critically ill men: effect of dopamine.

OBJECTIVE: Critical illness has been associated with decreased LH secretion and lowering of testosterone. Dopamine is often used for vasoactive support in these patients. We therefore aimed to investigate LH secretion during severe illness and particularly the effect exerted by dopamine on LH in such patients. PATIENTS AND DESIGN: In a randomized, controlled study of critically ill adult male polytrauma patients (n = 9), we evaluated the effect of prolonged (83-296 hours) dopamine infusion (5 micrograms/kg/min i.v.) on the dynamics of LH secretion and on serum testosterone concentrations. The effect of brief (15-21 hours) dopamine administration was documented in an additional randomized, controlled, cross-over study involving 6 patients. MEASUREMENTS: Serum LH concentrations were measured by IRMA. The LH profiles, obtained by blood sampling every 20 minutes for 9 hours during two consecutive nights, were examined by deconvolution analysis. Serum testosterone concentrations were measured by RIA once per study night. RESULTS: We found that before dopamine initiation and within 24 hours of dopamine withdrawal, the mean serum LH concentrations, the LH secretory amplitude, the amount of LH secreted per burst, the mean LH secretion rate and the number of LH pulses were higher than during dopamine infusion, being increased by a median of 161% (P = 0.006), 98% (P = 0.03), 106% (P = 0.03), 164% (P = 0.01) and 25% (P = 0.008) respectively. However, without dopamine administration the amplitude and mass of the LH secretory bursts still appeared to be low, whereas the pulse frequency remained elevated. After dopamine withdrawal, LH secretion increased significantly within 3 hours. Serum testosterone levels were very low and dopamine infusion appeared not to affect them within 24 hours. CONCLUSION: We documented decreased LH secretory pulse amplitude and mass with increased pulse frequency, as well as very low serum testosterone concentrations in critically ill men. Dopamine infusion further suppressed LH release by decreasing secretory burst amplitude, mass and frequency, possibly through an inhibitory action at both the pituitary and the hypothalamic level.

Adolescent↗
PubMed1983

Effects of testosterone, dihydrotestosterone and estradiol on gonadotropin release after gonadotropin releasing hormone administration in cyclic mares.

Sixteen intact cyclic mares were treated on the fourth day of estrus and then every other day for a total of six injections with 1) testosterone propionate, 2) dihydrotestosterone (DHT) benzoate, 3) estradiol (E2) benzoate or 4) safflower oil. Mares were given gonadotropin releasing hormone (GnRH) on Day 3 of estrus (pretreatment) and again 24 h after the last steroid or oil injection. Treatment with testosterone propionate resulted in a greater (P less than 0.05) follicle-stimulating hormone (FSH) response to the second injection of GnRH compared with all other treatments. Treatment with DHT benzoate also resulted in greater (P less than 0.05) FSH response to GnRH compared with control and E2 benzoate-treated mares. Testosterone propionate and E2 benzoate administration suppressed (P less than 0.05) the normal diestrous rise in FSH concentrations exhibited by the control and DHT benzoate-treated mares. Steroid treatment did not affect the luteinizing hormone (LH) response to GnRH, although testosterone propionate treatment did suppress concentrations of LH in daily blood samples during Days 3 to 6 of treatment. It is concluded that testosterone's effect on FSH after GnRH treatment observed in this and previous experiments can be attributed to two different properties of the hormone or its metabolites acting simultaneously. That is, testosterone increased the secretion of FSH in response to GnRH as did DHT (an androgenic effect). At the same time, testosterone suppressed FSH concentrations in daily blood samples in a manner identical to that of E2 benzoate (an estrogenic effect).

Animals↗
PubMed1992

Somatic afferent regulation of plasma luteinizing hormone and testosterone in anesthetized rats.

The effects of cutaneous stimulation on plasma luteinizing hormone (LH) and testosterone were examined in adult male Wistar rats anesthetized with pentobarbital. Under the resting condition without somatic sensory stimulation, plasma LH and testosterone measured every 30 min between 1400 and 1730 h revealed no significant fluctuations. Nociceptive mechanical stimulation of bilateral hindpaws by pinching for 10 min significantly increased plasma LH and testosterone. Plasma LH was increased 30 and 60 min after stimulation, while plasma testosterone was increased 60-150 min after stimulation. However, innocuous mechanical stimulation of bilateral hindlimbs by brushing for 10 min did not significantly change either plasma LH or testosterone. These results indicate that, when emotional factors were eliminated by anesthetization, cutaneous nociceptive information led to the increased secretion of LH from the anterior pituitary, resulting in an increase in testosterone secretion from the testes into the plasma.

Animals↗
PubMed1988

Testicular involvement in peripubertal gonadotropin levels and accessory sex organ weight of male hamsters.

This study evaluates the influence of testicular secretions during development in male hamsters on peripubertal gonadotropin levels. Castration or sham operations were performed on the day of birth (Day 1), Day 5, 10, or 20 of life. Repeated plasma samples on Days 20-60 at 10-day intervals were taken via orbital sinus puncture. Castrated animals received a subcutaneous testosterone capsule on Day 60 and were killed on Day 70. In addition, seminal vesicles and ventral prostate weights were taken in all animals at Day 70. Castrated animals, regardless of day of castration, had higher gonadotropin levels and suppressed sexual accessory organ weights. Animals castrated on the day of birth had lower luteinizing hormone (LH) levels than animals castrated on other days. Castration on Day 10 resulted in lower follicle stimulating hormone (FSH) levels. Males castrated on Day 20 were most sensitive to the negative feedback effect of testosterone on LH secretion, while Day 10 castrates had elevated FSH levels after testosterone exposure. Sexual accessory weights also differed depending upon the day of castration. Results point out the importance of testicular secretions on the developmental processes as well as the differing ages at which various systems may be influenced.

Animals↗
PubMed1997

Effects of prenatal testosterone on sexual behavior, reproductive morphology and LH secretion in the female rat.

Sexual differentiation of many brain structures and functions is dependent on levels of testosterone (T) or its metabolites during certain 'sensitive' developmental periods. If T is present during these perinatal periods, masculinization and defeminization of sexual behavior occur; also, reproductive physiology, and central nervous system morphology and function are altered. The purpose of the present study was to characterize the influence of T at specific prenatal developmental intervals on offspring reproductive morphology, physiology, locomotor activity and sexual behavior during postnatal development. To avoid complications induced by endogenous testicular activity, only females were examined. Free T was used because of its relative short half-life, so that the effects induced by its administration on a specific gestational day (GD) could be evaluated. Pregnant rats received a single subcutaneous injection of either sesame oil (controls) or 5 mg of T on GD 16, 17, 18, 19, 20, 21, or 22. Female offspring of pregnant rats exposed to T displayed significant alterations in morphology and behavior. The anogenital distance, measured at 25 days postbirth, was significantly increased if T was administered on GD 16, 17 or 18. T treatment on GD 16 or each day thereafter through GD 20 significantly delayed the normal occurrence of vaginal opening (controls at 37.5 days vs. T treatment which ranged from 38.5 to 41.4 days). Abnormal vaginal morphology (enlarged clitoris) was also observed when T was injected during a similar prenatal interval (i.e. GD 16 to GD 22). Furthermore, prenatal T treatment on GD 18 (and each day thereafter), until GD 22 significantly decreased lordotic behavior compared to control values. However, exposure to T, on any prenatal GD did not alter the animals' ability to exhibit an induced luteinizing hormone (LH) surge. These results suggest that the onset for altered reproductive morphology occurs at least as early as GD 16, whereas the onset of sexual behavior sensitivity occurs precisely at GD 18, and that the normal pattern of adult LH release in females is not altered by prenatal androgen treatment using this specific paradigm.

Animals↗
PubMed1992

[The effect of thyroid- and sex hormones on triglyceride secretion in rat liver].

The influence of thyroxine, estradiol and testosterone on the triacylglycerol (TG) secretion rate out of the liver into the blood as well as on concentrations of FFA, triglycerides, and glucose in serum was determined. All of these experiments were carried out under different nutritional conditions (non-fasting, and 10 or 16 h fasting, respectively). Accordingly the results after hormone application were compared with three groups of controls. Within these control groups increasing time of fasting caused exclusively an enhancement of FFA concentrations, while the TG secretion rate and other parameters were not influenced. Concerning all hormones effects on several lipid parameters have been observed. In particular, a decrease of FFA concentrations in comparison with controls after 16 h fasting was evident. In these cases, the TG secretion rate and TG concentration in serum were simultaneously lowered. Both alterations may be a consequence of a diminished mobilization of FFA in adipose tissue. Increases of FFA concentrations in serum after hormone application, compared with the corresponding controls, only occurred after administration of thyroxine and testosterone, while changes of the TG secretion rate and the TG concentration in serum were scarcely observed. Final remarks about the actual influence of hormones on the investigated parameters, especially TG secretion rate were drawn including results of a previous paper, where catecholamines, insulin, and prednisolone had been tested under the same conditions.

Adipose Tissue↗
PubMed1986

[Mediated action of phytogenic antineoplastic agents on rats with Pliss lymphosarcoma].

The action of drugs of plant origin and of alkylating compounds (sarcolysine, prospidin) was accompanied by hormonal changes in rats with inoculated Pliss' lymphosarcoma. After the use of polyphenol plant drugs the secretion of pituitary FSH was inhibited, the blood concentration of testosterone was reduced and the cortisol secretion was substantially increased. The alkylating compounds stimulated the production of FSH, increased the secretion of testosterone, and clearly lowered the cortisol level.

Animals↗
PubMed1989

Maintenance of testosterone production by purified adult rat Leydig cells for 3 days in vitro.

Using a preparation of highly purified, adult rat Leydig cells and conditions of culture which we found to optimize testosterone production during 24 h, we sought to maintain optimal testosterone production for 3 d. Leydig cells cultured on Cytodex 3 beads at 19% O2 in Dulbecco's modified Eagle's medium-Ham's nutrient mixture F12 (1:1; vol/vol) containing 0.5 mg/ml total bovine lipoproteins (less than 1.222 g/ml) with maximal luteinizing hormone (LH) stimulation failed to maintain a constant amount of testosterone for 3 d. These cells did however secrete a similar amount of total delta 4-3-ketosteroids on each of the 3 culture d, indicating that their viability was preserved. The predominance of progesterone and 170H-progesterone relative to the amount of androstenedione found on Days 2 and 3 suggested that the activity of the cytochrome P450 C17-hydroxylase-C17,20-lyase enzyme in the smooth endoplasmic reticulum was diminished when Leydig cells were maintained in our primary culture for longer than 24 h. Decreasing the oxygen tension of the cultures from 19 to 5%, and decreasing the concentration of LH used to stimulate the Leydig cells from 100 to 0.1 ng/ml, were necessary to achieve maintenance of testosterone secretion without accumulation of other delta 4-3-ketosteroids during a 3-d period. Cells cultured in this fashion were still able to respond to maximal LH stimulation during Day 3, producing as much testosterone as if cultured for 24 h on Day 1 at 19% O2 with 100 ng/ml LH stimulation.

17-alpha-Hydroxyprogesterone↗
PubMed1986

Cell interactions in the rat seminiferous epithelium with special reference to the cellular distribution of calmodulin.

Spermatogenesis is dependent on stimulation by pituitary gonadotropins, FSH and LH. Targets for these hormones are Sertoli and Leydig cells, respectively. The effect of LH on spermatogenesis is mediated by testosterone. In addition to hormones, interactions between neighbouring cells seem to regulate spermatogenesis. This is reflected by cyclic secretion of several proteins by the seminiferous epithelium, of which plasminogen activator is a good example. While it is controlled by FSH a factor in preleptotene spermatocytes may also influence its cyclic secretion pattern. Both testosterone and FSH have a cyclic action in the seminiferous epithelium. The androgens seem to predominate in stages where spermiation, onset of meiosis and the highest rate of RNA transcription occur (VII-XI). FSH is most active in stages that contain meiotic divisions and early spermiogenesis (XIII-V), greatly stimulating the production of cyclic AMP. To investigate further the "second messengers" of FSH action in the seminiferous epithelium, the cellular distribution of calmodulin was analyzed using an indirect immunocytochemical method. In addition to their clear cyclic distribution in primary spermatocytes and in spermatids, Sertoli cells also showed a bright calmodulin immunofluorescence that was apparently cyclic. These observations suggest a local calmodulin and calcium regulation of spermatogenesis.

Androgens↗
PubMed1990

Pulsatile secretion of luteinizing hormone in agonadal men before and during testosterone replacement therapy.

UNLABELLED: We have reevaluated the question regarding the pulsatile pattern of LH secretion in agonadal men before and following testosterone replacement therapy. Five normal males were used as a reference group and four agonadal men were studied before and during replacement therapy with testosterone enanthate. All the subjects were sampled every 5 min for 12 h (08:00 to 20:00). Data were analyzed using the statistically based and validated pulse detection program DETECT. The normal subjects showed an LH pulse frequency of 10.2 +/- 1.7 peaks/12 h (mean +/- SEM) and a mean duration of 48.8 +/- 14 min, while in agonadal patients without testosterone replacement the frequency of LH peaks (27.5 +/- 2 peaks/12h) was significantly higher than for normal subjects (p less than 0.05), and the mean duration of peaks was lower than in controls (17.2 +/- 1.2 min; p less than 0.01). Following chronic testosterone enanthate replacement therapy (200 mg im every two weeks) these patients showed an increase in the duration and a significant reduction in the frequency of LH peaks (from 27.5 +/- 2 to 18.2 +/- 2.1 peaks/12 h; p less than 0.01) but pulse frequency remained significantly higher than for normal subjects (p less than 0.01). This finding is independent of the choice of p values for false positive detection rate (p = 0.01 or p = 0.005), but it does depend on sampling frequency and is influenced by large (four-fold) changes in the thresholds for peak detection. Using a "discrete deconvolution" technique we estimated the instantaneous secretory rate (ISR) for the two groups of patients. The results using ISR corroborated the findings obtained using analysis of observed plasma LH measurements. ISR computation also showed that the duration of the secretory events of the gonadotropes is significantly shorter (p less than 0.01) than the one estimated on plasma concentration, both in normal subjects and in agonadal patients before and during testosterone administration. IN CONCLUSION: LH pulse frequency observed in basal conditions in agonadal men was much higher than previously reported in primary testicular failure; during conventional testosterone replacement therapy LH pulse frequency of agonadal men was significantly reduced but still higher (p less than 0.01) than in normal men. This finding is probably related to the subnormal plasma levels of testosterone found in agonadal men during the replacement therapy; the analysis of data using a sampling interval of 10 min gave results similar to previous reports, confirming that the choice of sampling interval can markedly affect the evaluation of frequent LH pulsatile secretion.

Adult↗
PubMed1990

The pulsatile secretion of bioactive luteinising hormone in normal adult men.

We have studied bioactive and immunoreactive LH pulsatility in 11 normal men. The temporal relationship of plasma LH, testosterone, and FSH were also investigated. Blood samples were taken at 10-minute intervals for 6 h and bioactive LH levels were determined using an in vitro mouse Leydig cell bioassay. Testosterone, LH and FSH were determined by standard radioimmunoassay. Twenty-two bioactive LH pulses were detected (amplitude 8.5 +/- 4.9 IU/l, mean +/- SD) with a frequency of 2 +/- 0.8/6 h compared with only 18 immunoreactive LH pulses (amplitude of 3.6 +/- 1.8 IU/l) and a frequency of 1.6 +/- 0.5/6 h. Bioactive:immunoreactive LH ratios increased (p less than 0.01) from the preceding pulse nadirs (2.26, range 1.66-4.28) to the pulse peaks (2.71, range 1.99-4.67). Twenty FSH pulses (seen in all but one subject) of low amplitude (0.7 +/- 0.6, median 0.5 IU/l) were also present. There was a close temporal relationship between testosterone and FSH secretion with bioactive and immunoreactive LH pulses with lags of 30-60 and 0 min, respectively. We conclude that immunoreactive LH pulses are discordant from bioactive LH pulses in 18% of occasions. Further, the mean amplitude of bioactive episodes were approximately 2.6 times greater than that of immunoreactive episodes, whereas interpulse period and pulse duration were similar. The increase in bioactive:immunoreactive ratio at pulse peaks may indicate that in normal men LH pulses are enriched with a more biopotent form of the molecule.

Adult↗
PubMed1978

Androgen, estrogen, and progesterone by a lipid cell tumor of theovary.

In a 64-year-old woman with a virilizing lipid-cell tumor of the left ovary, serum progesterons, androgens, estrogens, and cortisol levels in the peripheral and ovarian veins were measured. Although virilization was the only symptom of hormone production by the tumor in this patient, endocrine studies showed that several steroids were secreted by this neoplasm. Of the steroids measured, androstenedione was the principal secretory product. Pregnenolone, 17-hydroxypregnenolone, 17-hydroxyprogesterone, dehydroepiandrosterone, and testosterone were also secreted, but in quantities which were one third to one sixth the amount of androstenedione. The tumor's pattern of hormone secretion was similar to patterns of steroid production by ovarian stromal cells found in previously reported in vitro studies. This case and a review of the literature demonstrate that androstenedione appears to be the predominant secretory product of lipid cell tumors, whereas testosterone is the predominant secretory product of hilus cell tumors.

17-alpha-Hydroxypregnenolone↗