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

Abstract

ABSTRACT The content and concentrations of immunoreactive LH (LER-960) and FSH (LER-869) were determined in 79 human foetal pituitary glands from 68 days of gestation to term, and in the pituitary glands of 3 anencephalic infants, 10 infants and children 2 weeks to 7 years of age, and 4 adults. In addition, the concentration of immunoreactive serum LH, FSH, LH-HCG, and HCG was determined in 48 foetuses and 6 anencephalic infants. The mean content of LH in the pituitary glands of the female foetuses increased sharply from 88.2 ± 44.2 ng at 10 to 14 weeks to 4983.8 ± 1128.4 ng at 25 to 29 weeks of gestation. In the male foetuses, the mean content of pituitary LH rose from levels of 21.0 ± 11.6 ng to peak levels of 114.5 ± 57.1 ng at 20 to 24 weeks of gestation. The concentration of LH in the pituitary glands of the children was comparable to that of foetuses at mid-gestation. The mean content of FSH in pituitary glands of female foetuses rose from 7.4 ± 5.2 ng at 10 to 14 weeks to 4788.6 ± 1460.7 ng at 25 to 29 weeks of gestation. In the male foetuses the pituitary content rose from 1.8 ± 0.7 ng at 10 to 14 weeks to 149.5 ± 69.1 ng at 25 to 29 weeks of gestation. The differences in pituitary content of LH and FSH between the male and female foetuses were highly significant from 15 to 29 weeks 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 as early as 84 days of gestation at a concentration of 11.0 ng/ml (LER-869). Serum FSH rose to peak levels (18.2 ± 3.6 ng/ml) at 20 to 25 weeks in a range comparable to that of castrate adults. A decrease was noted by 30 to 34 weeks to levels of 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 foetus. Immunoreactive LH was present in high concentrations by 99 days of gestation (21.5 ng/ml LER-960). Peak levels were attained by 100 to 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 βHCG radioimmunoassay decreased from the relatively high levels in foetuses at 90 to 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. These data suggest a sex difference in the synthesis and secretion of FSH and LH by the pituitary gland in the human foetus. 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 foetal life. While the foetal pituitary gonadotrophins do not seem to play a role in the sex differentiation of somatic sex structures in man, the evidence supports an effect on the development of the gonads in females and males and of the differentiated genital tract in the male.