ExtractNineteen male subjects were given five daily injections of 17P-estradiol and circulating levels of estradiol (E,), testosterone (T), and gonadotropins were determined by radioimmunoassay before, during, and after the steroid course. Peak levels of E, attained during the 5 days of treatment ranged from 173-577 pg/ml. Four of seven normal adult men and one castrate man demonstrated suppression of follicle-stimulating hormone ( FSH ) and luteinizing hormone (LHI with a subseauent rise in LH (oositive feedback) while E, levels remained elevated. A rise in T ;is associated with the L H increment in the four normal men. Nine pre-, early, or midpubertal boys and two men with hypogonadotropic hypogonadism displayed only gonadotropin soppressiorl after E, administration. The difference in LH response to estrogen (i.e., positive feedback) between the adult men with normal or elevated gonadotropin levels as compared with the endocrinologically normal boys is significant ( P < 0.01 ).
SpeculationPositive feedback between estrogen and 1.H is present in intact adult men, although the magnitude and consistency of this response is less than in women. Testosterone in men may act like progesterone in the female rhesus monkey to blunt the magnitude of the L H rise during estrogen administration. The potential for positive feedback appears to be a maturational event occurring during puberty in men as well as in women.Sexual differentiation of the brain and the consequent ability of the female of the species to exhibit regular ovulatory cycles exists in certain rodents and can be influenced by neonatal exposure to a number of steroid hormones. In contrast, fetal and neonatal exposure of the brain of the rhesus monkey to gonadal steroids does not appear to influence the basic hypothalamic mechanisms controlling reproduction (4).The ability of estrogen to induce the release of LH, termed positive feedback, has been demonstrated in the intact, adult female and in the postpubertal, castrate male, and female rhesus monkey (18). Such effects of estrogen have not been found in the intact, adult male rhesus. LH re!ease after estrogen administration has also been demonstrated in adult women (9, 11) but not in sexually immature girls ( I I). The onset of positive feedback appears to be a late pubertal event in the female (I I). We should like to present evidence that a stimulatory luteinizing hormone response to exogenous estrogen is also a maturational event in men.
M A T E R I A L S A N D M E T H O D S SUBJECTSSeven normal, adult men (ages 20-22) and one male (age 21) with the syndrome of vanishing testes (1) were hospitalized for study at the Clinical Center of the National Institutes of Health. Each patient was given five daily intramuscular injections of 10 or 15 pg/kg body weight of 17P-estradiol (E,) (20) and blood samples were obtained every 12-24 hr before, during, and after the estrogen course (see Table 1).Nine endocrinologically normal boys between the ages of 7 and 18 were studied in the course of evaluation for short stat...