Clomiphene citrate was administered to mature female rats at 5 dose levels for 16 days and pituitary thyrotropin levels were measured as well as indices of thyroidal and gonadal function. Thyroidal 131I uptake was increased, serum free thyroxin was reduced and PBI remained unchanged. A marked increase in pituitary TSH occurred. Estrous cycles were blocked and uterine weights reduced, however, no significant change was seen in ovarian weights except for reduction at the highest dose of clomiphene. Clomiphene depressed the usual thyroidal weight response to TSH when added to bovine thyroid slices invitro. The results suggests that clomiphene has direct effects on thyroidal iodide uptake and T4 secretion, probably unrelated to direct central effects on pituitary TSH secretion.
The effects of FSH, HCG, GH and testosterone on testicular protein synthesis were investigated in hypophysectomized adult mice by measuring the incorporation of tritiated lysine into acid-precipitable material. The incorporation per mg protein was increased by FSH, HCG and GH but decreased by testosterone. The maximum effect of FSH occurred at between 8 and 14 h after administration of the hormone, much later than found in vitro for the rat.
In-vivo testicular binding of highly purified pituitary FSH, labelled by a method which did not significantly affect biological potency, was hormone-specific, tissue-specific and dose-dependent. Hypophysectomy of mice was followed by a progressive increase in the amount of 125I-labelled FSH per unit weight of testis but not in the total amount of hormone taken up by the testis. Maximum binding occurred at 4 h in a membrane-containing fraction prepared by high-speed ultracentrifugation of testicular homogenate. This is considerably later than has been reported for testicular tissue incubated in vitro at 37 degrees C.
Human pituitary FSH increased the incorporation of [5-(3)H]uridine into RNA in vivo in the testes of intact 9-day-old mice and of hypophysectomized adults. In both groups the effect was greatest 8 h after administration of 5--7.5 i.u. FSH. Autoradiographs were prepared from the testes of hypophysectomized adult mice given subcutaneous injections of FSH or of 0.9% saline 6 h, and [5-(3)H]uridine 1.5 h, before death. Treatment with FSH caused statistically significant increases in the density of silver grains over the nuclei of Sertoli cells, type A and intermediate spermatogonia, and preleptotene and mid-pachytene primary spermatocytes. It was concluded that FSH has a generalized stimulatory action on RNA synthesis in the nuclei of Sertoli cells and those types of germinal cell which synthesize RNA most actively.
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