Increase In FSH Secretion Research Articles

Clomiphene Citrate and Its effects Upon Ovulation and Estrogen

This paper reports a clinical evaluation of the mechanism of action of clomiphene citrate and describes selection of the most responsive patients. Patients were 121 women, aged 21-37 years, who desired pregnancy. Their infertility was diagnosed as being due to anovulation. Primary amenorrhea or special endocrine disorders were not present. All the women who had no vaginal bleeding for more than 2 months were diagnosed amenorrhea and treated with 65 mg of progesterone capronate intramuscularly. They were then divided into two subgroups on the basis of the presence or absence of vaginal bleeding within 2 weeks. Clinical studies included: basal body temperature charts; daily vaginal smears evaluated by the ink acidophilic stain index (ISI); cervical mucus evaluated by amount, spresence of spinnbarkeit, and ferning; 24-hour urines examined for estrogen and total gonadotropic activity; and a pregnanediol determination. Each group received daily 50 mg doses of clomiphene citrate for 5 days. Estrogen inhibiting effect of the drug was suggested by vaginal cytology and the disappearance of ferning and decrease in quantity of cervical mucus. However, the excretion of the total urinary estrogen was increased in ovulatory cases (81 of the 121 patients). In 17 patients having no bleeding within 2 weeks after progesterone injection no ovulation could be induced. In patients with withdrawal flow 54 of 70 achieved ovulation. Of 37 patients with previous anovulatory bleeding 27 achieved ovulation. There were 11 of the 121 who became pregnant. In those with early ovulation the antiestrogen effect is believed to be in the hypothalamus and pituitary bringing about the estrogen surge and stimulating LH secretion. In those with later ovulation the antiestrogenic effect increased FSH secretion followed by ovulation. The type of patient most likely to respond to clomiphene citrate is one with nearly normal pituitary-gonadal axis. Inducing withdrawal bleeding with progesterone in those amenarrheic patients who are to be treated with clomiphene citrate is believed to be a good method of anticipating the result of the treatment.

The effect of chemical ovulation-inducing substances on gonadotropin secretion in incubation experiments of the anterior pituitary.

In order to clarify the in vitro action of clomiphene, F 6066 and Lychium chinense Miller (LCM) on the pituitary, the anterior pituitary of the rat was incubated with these materials and the gonadotropin in the medium was assayed. 1) Clomiphene showed no increase of LH secretion upon its addition to the incubation medium containing the pituitary alone or in the presense of the hypothalamus. The addition of a large amount of clomiphene induced a slight increase in secretion of FSH but it was not statistically significant, while prolactin secretion was significantly stimulated by a small amount of clomiphene. Secretion of prolactin was stimulated even in the presence of the hypothalamus. 2) F 6066 acted directly on the pituitary, markedly stimulating LH secretion. No significant changes of FSH and prolactin values were observed. 3) Extracts from LCM acted directly on the pituitary to stimulate LH secretion. 4) The results described above suggest that both clomiphene and F 6066 act on the diencephalon-pituitary system. Clomiphene gives a more marked effect on prolactin, while F 6066 acts on LH secretion more strongly. The action of LCM to induce ovulation is presumably consisted of a direct action on the pituitary to induce LH secretion. Further studies are necessary to elucidate the mechanism of action of these substances.

HYPOPHYSEAL GONADOTROPHINS FOLLOWING GONADECTOMY IN MALE AND FEMALE ANDROGENIZED RATS.

ABSTRACT Male and female rats were androgenized by a single injection of testosterone (17β-hydroxy-androst-4-en-3-one) propionate on the 5th postpartum day. At 30 days of age, iittermates were joined in parabiosis and one partner gonadectomized. Gonadotrophin release by the hypophysis of the gonadectomized member was evaluated by effects upon weight and histology of gonads and sex accessories in the intact partner. A total of 80 pairs in 9 combinations were used. Single animals of the same age served as controls. The results demonstrate that androgenized males have reduced testes and accessory weights at 60 days. However, the treatment does not adversely affect production or release of hypophyseal FSH or LH following castration. In androgenized females, removal of the ovaries results in increased FSH secretion only.