Mridula Chowdhury

Unusual Anti-Reproductive Properties of the Analog [d-Leu6,Des-Gly- N H 2 10 ]-Luteinizing Hormone-Releasing Hormone Ethylamide in Male Rats *

Nanogram quantities of a luteinizing hormone-releasing hormone (LHRH) agonist, [D-Leu6,des-Gly-NH2(10)]-LHRH ethylamide, were injected into immature male rats twice daily for 40 days. Treatment with the analog significantly increased serum luteinizing hormone and follicle-stimulating hormone levels, but suppressed accessory sex organ weights. Plasma and testicular concentrations of testosterone were also significantly decreased. The agonist did not alter body, pituitary, or testis weights. Spermatogenesis and the morphology or density of the Leydig cells also appeared not to be affected. A possible direct effect of the analog on the testes is discussed.

Effect of Estradiol Benzoate on the Pituitary‐Gonadal Axis in the Intact Male Rat

Erwachsene männliche Ratten wurden 28 Tage lang täglich mit 50 μg Oestradiolbenzoat subcutan behandelt. Die Gewichte der Sexualorgane und der Hypophyse zeigten die für eine Oestrogenzufuhr klassischen Veränderungen. Sowohl die Plasma‐ als auch die Hoden‐Testosteronwerte gingen innerhalb von 24 Stunden nach der ersten Oestrogeninjektion auf fast Spurenwerte zurück und blieben dort während der Experimentierperiode. Die Hypophysen‐LH‐Werte und deren Konzentration zeigten einen progressiven Abfall; demgegenüber blieben die Plasma‐LH‐Werte während des Experimentes unverändert. Dieses Ergebnis legt es nahe, daß bei der gesunden männlichen Ratte das Oestrogen die Hoden‐Testosteron‐Produktion direkt beeinflußt. Die Beobachtung gibt Veranlassung für die Notwendigkeit einer Überprüfung der gegenwärtigen Vorstellungen über die Hoden‐Hypophyse‐feedback‐Mechanismen.

Effect of testosterone and estradiol on the basal and LRF-stimulated secretion of gonadotropins in pituitary cell culture.

The effect of testosterone and estradiol on the basal and LRF-stimulated secretion of gonadotropins was investigated utilizing monolayer cultures of rat anterior pituitary cells. Addition of synthetic LRF consistently yielded higher concentrations of radioimmunoassayable LH and FSH in both the medium and the cells. Testosterone (1μg/ml) or estradiol (0.5μg/ml) stimulated the basal release of both gonadotropins, but diminished the LRF-stimulated release of LH and FSH. The effect of testosterone on the basal or LRF-stimulated release of gonadotropins was more pronounced compared to estradiol. Estradiol diminished the LRF-stimulated increase of LH and FSH in the cells while testosterone had a similar effect on LH but not on FSH. Neither steroid, in absence of LRF, significantly altered the cellular content of LH, but testosterone slightly increased the FSH content.These results provide additional direct evidence for the effect of gonadal steroids on the basal and LRF-stimulated secretion of gonadotropins at ...

Sex Difference in de novo Synthesis of FSH in Developing Rats

A study of the FSH synthesis pattern in the maturing (10–40 days of age) male and female rats has been conducted. The plasma and pituitary FSH levels were measured by double antibody radioimmunoassay (RIA). De novo synthesis of FSH was studied by incubation of pituitaries with 3H-leucine and immunoprecipitation of the total FSH (including the newly synthesized hormone) with an FSH antibody. A marked difference in the pattern of changes in the pituitary and plasma levels and the de novo synthesis of FSH was noted between the two sexes. In the females the highest circulatory FSH levels were noted on the 10th day of life (2,009 ng NIHFSHS-1/ml). The level dropped progressively until the 30th day of age and remained approximately at the level of 500 ng/ml until the 40th day of age. Incorporation of 3H-leucine in the FSH molecules or the de novo synthesis of this hormone was also highest between the 10th and 15th days of age and gradually diminished until the 30th day when it leveled off. In the males the incorporation of 3H leucine increased gradually from 10 days of age and peaked on the 35th day at the same time that the highest FSH levels were observed in both serum and the pituitary. At the age of 40 days, the plasma and the pituitary FSH levels decreased, paralled to a decrease in synthetic rate. These data are interpreted to suggest that (1) the changes in the rates of FSH synthesis are primarily responsible for the dramatic changes in circulatory FSH levels, and (2) the factors which inhibit the release of FSH in these animals ultimately inhibit its synthesis as well.

Unusual Anti-Reproductive Properties of the Analog [d-Leu6,Des-Gly- N H 2 10 ]-Luteinizing Hormone-Releasing Hormone Ethylamide in Male Rats**Supported in part by National Institutes of Health Grant 5 P50 HD08338.

Nanogram quantities of a luteinizing hormone-releasing hormone (LHRH) agonist, [d-Leu 6 ,des-Gly- N H 2 10 ]-LHRH ethylamide, were injected into immature male rats twice daily for 40days. Treatment with the analog significantly increased serum luteinizing hormone and follicle-stimulating hormone levels, but suppressed accessory sex organ weights. Plasma and testicular concentrations of testosterone were also significantly decreased. The agonist did not alter body, pituitary, or testis weights. Spermatogenesis and the morphology or density of the Leydig cells also appeared not to be affected. A possible direct effect of the analog on the testes is discussed.

An Investigation of Plasma Hormone Levels Before and After Vasectomy**Supported by Contract NO1-HD-2-2776 from the Center for Population Research, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Md.††Presented in part at the Thirty-First Annual Meeting of The American Fertility Society, April 3 to 5, 1975, Los Angeles, Calif.

A prospective study of effects of vasectomy on the plasma levels of testosterone, estradiol, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) was instituted. Postvasectomy plasma hormone levels were compared with prevasectomy, base line levels. Beginning at 6 months after vasectomy, mean plasma testosterone levels demonstrated a statistically significant elevation, mean plasma estradiol levels were lower, mean plasma LH levels were elevated, and mean plasma FSH levels were unchanged. By 2 years after vasectomy, a slight plasma FSH elevation had occurred, plasma estradiol levels had returned to base line, and plasma testosterone and LH levels remained elevated. These changes, although significant statistically, did not exceed the normal ranges found in normal adult males in our laboratory and were of unclear physiologic significance. Thus, it can be concluded from this study of 56 men studied for 2 years, 148 men studied for 1 year, and 182 men studied for 6 months after vasectomy that no adverse hormonal effects of vasectomy have been demonstrated.

Rapid Oscillations in Plasma Levels of Testosterone, Luteinizing Hormone, and Follicle-Stimulating Hormone in Men*†*Presented in part at the 29th Annual Meeting of The American Fertility Society, April 5 to 7, 1973, San Francisco, California.†Supported in part by a grant from The Ford Foundation.

A study designed to define the oscillatory pattern of plasma levels of testosterone luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in 4 young adult men was carried out. Blood samples were obtained every 2 minutes for 8 hours from the 3 normal and 1 oligospermic subjects. In each subject a different pattern of changes in hormone levels was found. In Subject 1 the predominant pattern was a slow sinusoidal fluctuation in testosterone levels. In Subject 2 changes in LH levels were the predominant finding. Subject 3 showed irregularly occurring FSH peaks that exceeded the coefficients of variation and which could have been undetected if less frequent sampling had been employed. Subject 4 the oligospermic volunteer demonstrated marked fluctuations in both FSH and LH. His LH levels were the highest and his FSH levels showed a regular sinusoidal pattern with a periodicity of approximately 30 minutes. In all subjects rapid variations in plasma testosterone levels were noted. No correlation was apparent between the levels of the 3 hormones in any of the subjects. It is concluded that although the observations made in the study cast doubt on the present concepts of negative feedback control of the pituitary-testicular axis additional studies are necessary to establish the physiological significance of the rapid oscillations in levels of plasma testosterone LH and FSH.