THE ONTOGENESIS OF HUMAN FOETAL HORMONES. II. LUTEINIZING HORMONE (LH) AND FOLLICLE STIMULATING HORMONE (FSH)

Abstract

Content and concentrations of immunoreactive LH [luteinizing hormone] (LER-960) and FSH [follicle stimulating hormone] (LER-869) were determined in 79 human fetal pituitary glands from 68 days of gestation to term and in pituitary glands of 3 anencephalic infants, 10 infants and children 2 wk-7 yr of age and 4 adults. The concentration of immunoreactive serum LH, FSH, LH-HCG [luteinizing hormone-human chorionic gonadotropin] and HCG was determined in 48 fetuses and 6 anencephalic infants. The mean content of LH in the pituitary glands of female fetuses increased sharply from 88.2 .+-. 44.2 ng at 10-14 wk to 4983.8 .+-. 1128.4 ng at 25-29 wk of gestation. In male fetuses the mean content of pituitary LH rose from 21.0 .+-. 11.6 ng to 114.5 .+-. 57.1 ng at 20-24 wk of gestation. The concentration of LH in the pituitary glands of the children was comparable to that of fetuses at mid-gestation. The mean content of FSH in pituitary glands of female fetuses rose from 7.4 .+-. 5.2 ng at 10-14 wk to 4788.6 .+-. 1460.7 ng at 25-29 wk of gestation. In male fetuses the pituitary content rose from 1.8 .+-. 0.7 ng at 10-14 wk to 149.5 .+-. 69.1 ng at 25-29 wk of gestation. Differences in pituitary content of LH and FSH between male and female fetuses were highly significant from 15-29 wk of gestation. The correlation of the incremental changes in the pituitary content of LH and FSH with gestational age was significant (P < 0.02). Immunoreactive serum FSH was detected at 84 days of gestation at 11.0 ng/ml (LER-869). Serum FSH rose to 18.2 .+-. 3.6 ng/ml at 20-25 wk, in a range comparable to that of castrate adults, and decreased by 30-34 wk to 1.7 .+-. 0.05 ng/ml, comparable to that in cord samples at term (1.8 .+-. 0.2 ng/ml). A significant negative correlation with gestational age was shown after the mid-gestational period (P < 0.01). Immunoreactive LH, measured by a specific LH assay, was unaffected by levels of HCG present in the fetus. Immunoreactive LH was present in high concentrations by 99 days of gestation (21.5 ng/ml LER-960). Peak levels were attained by 100-180 days of gestation with a decrease at them to less than 1.0 ng/ml. A significant negative correlation was noted between serum LH and gestational age. Serum HCG quantified in a .beta.HCG radioimmunoassay decreased from the relatively high levels in fetuses at 90-120 days gestational age to term. The mean concentration in umbilical cord sera was 268.5 .+-. 161 mIU/ml in contrast to 5400 .+-. 200 mIU/ml in maternal plasma at term. A sex difference in the synthesis and secretion of FSH and LH by the pituitary gland in the human fetus is suggested. This sequential pattern of change in the concentration of both serum and pituitary LH and FSH is consistent with the development of a functional hypothalamic pituitary gonadal negative feedback system during fetal life. While the fetal pituitary gonadotrophins do not seem to play a role in the sex differentiation of somatic sex structures in man, an effect on the development of the gonads in females and males and of the differentiated genital tract in the male is supported.