Maturation of Hypothalamic-Pituitary-Gonadal Function in Normal Human Fetuses: Circulating Levels of Gonadotropins, Their Common a-Subunit and Free Testosterone, and Discrepancy between Immunological and Biological Activities of Circulating Follicle-Stimulating Hormone*

Abstract

The recent availability of both cordocentesis, a low risk and effective technique for fetal blood sampling, and ultrasensitive/highly specific two-site immunofluorometric assays (IFMA) for pituitary and chorionic glycoprotein hormone (I-LH, I-FSH, and I-CG) measurement prompted us to study the maturation of hypothalamic-pituitary-gonadal function in 114 normal human fetuses (49 females and 65 males) from 17-40 weeks gestation. The subjects were selected from 216 consecutive cordocenteses carried out for rapid karyotyping and diagnosis of fetal infection or hematological disorders. In addition, FSH bioactivity (B-FSH) was measured by rat Sertoli cell aromatase induction assay, glycoprotein hormone alpha-subunit (alpha-SU) by RIA, and circulating free testosterone (fT) by direct analog technique. No significant cross-reactions were recorded in the different measurement methods. In particular, alpha-SU did not interfere in any IFMA, and CG cross-reactivity in LH IFMA was 0.5%. Circulating I-LH, I-FSH, and B-FSH levels at 17-24 weeks gestation were significantly higher in female than in male fetuses (I-LH, 48 +/- 4 vs. 6.3 +/- 0.7 U/L; I-FSH, 35 +/- 2 vs. 0.7 +/- 0.1 U/L; B-FSH, 131 +/- 17 vs. 43.4 +/- 5.4 U/L). During the last weeks of gestation, a significant decrease in I-LH and I-FSH levels was seen in both female and male fetuses (I-LH, 0.24 +/- 0.05 and 1.0 +/- 0.3 U/L; I-FSH, 0.45 +/- 0.1 and 0.5 +/- 0.1 U/L), while serum B-FSH remained elevated, but the previously recorded difference between sexes disappeared (54.3 +/- 7.2 and 58.7 +/- 7.3 U/L). Circulating I-CG and alpha-SU levels at midgestation were elevated in both female and male fetuses (I-CG, 117 +/- 29 and 191 +/- 44 U/L; alpha-SU, 143 +/- 16 and 105 +/- 9 micrograms/L, respectively) and decreased thereafter (I-CG, 42 +/- 9 and 26 +/- 6 U/L; alpha-SU, 60 +/- 15 and 37 +/- 6 micrograms/L). Serum fT levels at midgestation were significantly lower in females than in males (4.3 +/- 0.9 vs. 10.0 +/- 0.8 pmol/L) and increased until term, when the difference between sexes disappeared (16.2 +/- 1.8 vs. 17.6 +/- 1.6 pmol/L).(ABSTRACT TRUNCATED AT 400 WORDS)

Timing of fetal exposure to stress hormones: Effects on newborn physical and neuromuscular maturation

“…Further, human fetal plasma testosterone has been significantly correlated with fetal plasma cortisol and male fetuses have significantly higher testosterone concentrations than female fetuses (Gitau, Adams, Fisk, & Glover, 2005). Higher concentrations of testosterone among male fetuses appear to be restricted to earlier periods of gestation, given that testosterone concentrations increase throughout gestation among female fetuses and are similar in the two sexes by term; therefore, the responsiveness of male fetuses to stress hormones in the current study could be due to baseline higher concentrations of fetal cortisol and testosterone earlier in gestation (Beck-Peccoz et al, 1991;Gitau et al, 2005).…”

Expression of Asialoglycoprotein Receptor in Human Fetal Liver.

“…The ASGP receptor in human fetal liver may therefore be associated with cellular recognition and act in the regulation of the number of cells in the liver. With respect to the clearance tool of ASGPs, little evidence has been accumulated, but recent reports stating that bioactive FSH concentrations were significantly higher than immunoactive FSH in human fetus [36] and that the median charge of FSH isoforms in the serum was more acidic than that in the matching pituitary gland in sheep fetuses [37] indicate that the predominant form of serum FSH is sialylated, suggesting that ASGP receptor in fetal liver plays functional roles in the clearance of ASGPs from the circulation.…”

Mass spectrometry methods measured androgen and estrogen concentrations during pregnancy and in newborns of mothers with polycystic ovary syndrome

“…There are studies that suggest that maternal androgens from PCOS women are passed on to their offspring during gestation trough placental passage and could possibly contribute to higher androgen concentrations during gestation and at birth in PCOS offspring. Others speculate that more androgens are synthesized endogenously by the fetus of PCOS offspring (12,23,24,25,26). The aim of our study is to compare androgen and estrogen concentrations in maternal serum during gestation and in umbilical cord blood, between mothers with PCOS and their offspring compared to non-PCOS mothers and their offspring, using highly specific liquid chromatography tandem mass spectrometry (LC-MS/MS) methods.…”