Radioimmunoassay for human follicle-stimulating hormone: physiological studies.

Most of the information concerning secretion changes in follicle-stimulating hormone (FSH) in humans has been gained with relatively insensitive bioassays of concentrates of pools of urine. We have developed a sensitive and specific radioimmunoassay for FSH that is 500-1000 times more sensitive than the rat ovarianweight augmentation assay and which is capable of quantifying FSH in small volumes of serum. Anti-FSH was prepared by immunizing rabbits with an impure FSH preparation. The majority of antisera showed complete inability to distinguish LH, TSH, and FSH, illustrating the immunological similarities of these hormones. One antiserum was specific when used in a radioimmunoassay. Potency estimates by bioassay were in good agreement, with a single exception, with those obtained with the radioimmunoassay for 10 FSH-containing preparations. Highly purified LH gave a higher potency by immunoassay than by bioassay. Sera from eugonadal men contained 5-25 mIU/ml; sera from castrate men contained over 30 mIU/ml. Sera from eugonadal women contained 7-25 mIU/ml during the follicular phase and 5-15 mIU/ml during the luteal phase of the menstrual cycle. Sera from castrate or postmenopausal women contained 40-250 mIU/ml. FSH was measured throughout the menstrual cycle in 19 women. The general pattern that emerged is summarized as follows: there is a small early follicular phase rise in FSH, and then FSH is relatively constant until mid-cycle; in the majority of women a mid-cycle rise of FSH occurs coincidentally to the mid-cycle LH ovulatory peak; during the luteal phase FSH levels are relatively constant and lower than during the follicular phase. Nonsequential oral contraceptives containing estrogen and progestogen abolish these changes and FSH concentrations remain low throughout treatment. Treatment of castrate men and castrate or postmenopausal women with high doses of oral estrogens results in a fall of FSH to levels found in eugonadal men or women, but not to undetectable levels. Children less than 5 yr of age had undetectable FSH (< 5 mIU/ml).

Production rates and metabolic clearance rates of human follicle-stimulating hormone in premenopausal and postmenopausal women.

The production rates (PR) and the metabolic clearance rates (MCR) of human follicle-stimulating hormone (HFSH) were determined in six pre- and five postmenopausal women. Human FSH (PER-780) labeled with (131)I to specific activities of 50-150 muc/mug was used as a tracer. Both double antibody and trichloroacetic acid (TCA) precipitation techniques were used to determine HFSH-(131)I levels in infusate and plasma. In four of the subjects MCRs measured by both constant infusion and single injection techniques were the same. By constant infusion, plasma HFSH-(131)I levels reached equilibrium between 4-5 hr.MCRs in six premenopausal women were 14.2+/-1.1 (mean +/-SE) ml/min. MCRs in five postmenopausal women were 12.6 +/-1.1 ml/min. Simultaneous HFSH and human luteinizing hormone (HLH) MCRs were determined in a single patient using HFSH-(125)I and HLH-(131)I as tracers by both constant infusion and single injection methods. These studies showed that the MCR of HFSH was 10.8-11.1 ml/min, and the MCR of HLH was 18.5-19.4 ml/min. From these data and previous MCR and PR studies of HLH from this laboratory, it appears that the MCR of HFSH is about one-half that of HLH. Endogenous HFSH and HLH levels were measured by radioimmunoassay. The PRs of HFSH, calculated by the product of endogenous level and MCR, were 146 +/-27mU/min in the premenopausal women and 2141 +/-264 mM/min in the postmenopausal women. 24-hr PRs, based on these results, compared with reports of 24-hr urinary excretions of biologically active HFSH indicate that 3-5% of production is found in urine in biologically active form. After our single injections of HFSH-(131)I, 8-29% was recovered in urine over 24 hr.

Studies of the pituitary-Leydig cell axis in young men with hypogonadotropic hypogonadism and hyposmia: comparison with normal men, prepuberal boys, and hypopituitary patients.

Pituitary and gonadal function was studied in seven chromatin-negative men, ages 15-27 yr, with retarded sexual and somatic development, skeletal anomalies, and hyposmia. These hyposmic patients were compared with normal men, prepuberal boys and hypogonadal patients with hypopituitarism. The urinary follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels of hyposmic subjects were the same as those of normal boys and hypopituitary patients but significantly lower than those of normal men. Clomiphene citrate did not cause an increase in plasma FSH and LH levels in either hypogonadal group as it does in normal men. In contrast to hypopituitary patients, thyroid and adrenocortical function and release of growth hormone in the hyposmic subjects were normal. The plasma testosterone levels were equally low in prepuberal, hypopituitary, and hyposmic patients but were increased to a greater extent by human chorionic gonadotropin (HCG) treatment in prepuberal and hypopituitary subjects than in the hyposmic patients. Prolonged treatment with HCG has failed to return plasma testosterone levels to normal in two hyposmic patients. These observations suggest that there are defects of both pituitary and Leydig cell function in men with the syndrome of hypogonadism, skeletal anomalies, and hyposmia. They have impaired secretion of FSH and LH and a Leydig cell insensitivity to gonadotropin.