Some notes on the background of the isolation, determination of structure, synthesis, and early clinical trials of the luteinizing hormone- and follicle-stimulating hormone-releasing hormone

Abstract

Some notes on the background of the isolation determination of structure synthesis and early clinical trials of the luteinizing hormone (LH)- and follicle stimulating hormone-releasing hormone (FSH-RH) are presented. The solving of the thyrotropin releasing hormone structure made the work on the hypothalamus easier. After establishing that the 11 types of estrogen-progesterone combinations used in contraceptive pills did not suppress the stimulatory effects of LH-RH on the release of LH it was postulated that contraceptive steroids act mainly on the hypothalamus. And later it was shown that these steroids also act on the pituitary gland. This helped postulate that sex steroids may cause differential release of LH and FSH in response to LH-RH/FSH-RH. Immunologic studies led to the production of antisera to LH-RH and development of a radioimmunoassay for LH-RH. It was then shown that such antisera caused gonadal atrophy in male animals and blocked the release of LH and FSH and ovulation in cycling rats. The synthesis of various analogs of LH-RH enabled 2 classes of these compounds to be established: 1) stimulatory superactive analogs causing prolonged liberation of LH and FSH and 2) inhibitory analogs which block LH and FSH release and ovulation.