Modification of Pituitary Thyrotropin and Thyroid Activity in the Rat Following Administration of Clomiphene Citrate

Abstract

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.

Effect of Clomifene on Thyroid Function in Normal Men

“…These animal results by Geliert et al (1970) were compatible with our re¬ sults in normal males, showing an increased serum TSH on day 5 in Group 1, and in Group 2 an increased TSH response to iv TRH on day 12 as an in¬ dicator of an increased pituitary reserve of TSH. This did not seem to support the hypothesis of a diminished TSH production during clomifene treatment put forward by Ruiz-Velasco et al (1970).…”

“…In their study Geliert et al (1970) also found a significant reduc¬ tion in serum free thyroxine and an increased content of TSH in the pituitary of the rats, the latter dependent on the dose of clomifene. It was also shown that the stimulating effect of TSH on bovine thyroid tissue cultures could be inhibited in vitro by clomifene.…”

“…Animal experiments have shown that clomifene in rats provoked an ac¬ celerated uptake of radioiodine into the thyroid gland (Sato et al 1965;Geliert et al 1970). In their study Geliert et al (1970) also found a significant reduc¬ tion in serum free thyroxine and an increased content of TSH in the pituitary of the rats, the latter dependent on the dose of clomifene.…”

“…Experiments in animals, however, indicated that clomifene exerted an ac¬ tion on the hypothalamo-pituitary-thyroid axis, which could not directly be explained by the oestrogenic or anti-oestrogenic properties of clomifene (Sato et al 1965;Geliert et al 1970). …”