Studies on the luteinizing hormone- and follicle-stimulating hormone-releasing mechanism in the testicular feminization syndrome: Hypothalamic-pituitary responsiveness to clomiphene, luteinizing hormone-releasing hormone, gonadectomy, and sexual steroids

Abstract

The follicle-stimulating hormone (FSH) and luteinizing hormone (LH) secretory response to various stimuli was studied in 4 adult siblings with the complete form of testicular feminization. Before gonadectomy, the 4 patients had elevated serum levels of both LH and FSH. Clomiphene administered for 7 days did not change the serum levels of gonadotropins. LH-releasing hormone (LH-RH) administration resulted in FSH release above the range observed in normal adult men and women; however, the maximum LH increase was not different from that of normal adults. Gonadectomy elicited a further and significant elevation of both FSH and LH levels. After castration, serum levels of LH and FSH exhibited a further increase following LH-RH administration comparable quantitatively to that before castration. The FSH secretory response to LH-RH was greater than that of LH. The administration of progesterone alone to the 4 patients already castrated did not result in any major change in the serum levels of FSH and LH. Estrogen administration decreased the high levels of gonadotropins. The relative decrease for FSH was greater than for LH, and, when progesterone was given following 4 weeks of estrogen treatment, an increase in the serum levels of LH was found; there was also a small increase in FSH concentration. It is concluded from this study that in testicular feminization: (1) There is a partial gonadal feedback control of both FSH and LH secretion; (2) hypothalamic receptors are not sensitive to the stimulatory effect of clomiphene; (3) there is an unusually large amount of FSH released by the pituitary after intravenous LH-RH; (4) FSH and LH secretion are readily suppressed by estrogen administration; (5) there is a positive feedback effect of progesterone upon serum gonadotropins in estrogen-primed castrated patients with testicular feminization.