hCG Binding and Stimulation of Testosterone Biosynthesis in the Human Fetal Testis

Abstract

The role of hCG in the regulation of testicular steroid production in human fetuses from 14 to 20 weeks gestational age was studied. Saturable binding of 125I-hCG to testicular homogenates was demonstrated, and physiologic concentrations of hCG were able to stimulate testosterone formation in testicular minces without the addition of exogenous precursors. In five fetses of 16-20 weeks gestational age, the capacity to bind hCG varied from 25.6 to 42.2 pg/mg wet tissue. The association constant of binding was 1.07+/-0.12 X 10(10) M-1. Testicular minces from six other fetuses (gestational age 14-19 weeks) were incubated in the presence of concentrations of 0, 0.5, 5 or 50 ng/ml NIH-hCG (1 mg=10,000 IU), which are within the physiologic range. Preincubation of 30 min in excess buffer was necessary to observe clear differences in testosterone production rates between controls and hCG stimulated testicular tissues. The greatest increase in testosterone production occurred when the hCG concentration was increased from 0.5 to 5 ng/ml. Little additional stimulation was observed at a concentration of 50 ng/ml. Maximal production rates of up to 12 ng/mg tissue/h were seen. It is concluded that human fetal testes bind hCG, and that physiologic levels of hCG stimulate fetal testicular testosterone formation in vitro at this stage of gestation.

Fetal tissue can synthesize a placental hormone. Evidence for chorionic gonadotropin beta-subunit synthesis by human fetal kidney.

“…Although the mechanism of neoplastic elaboration of these proteins is unknown, some workers have postulated that this represents a reversion to fetal gene expression (2). In studying the physiologic role of hCG in the human fetuis, we found that the human fetal testes (3) and adrenal (4) responded to hCG administration with increased steroidogenesis in vitro. To determine the relative hCG content in the fetus, the hCG concentration in homogenates of various fetal tissues was measured using an hCG 1-subunit (,B-hCG) radioimmunoassay Received for publication 23 10% in NET buffer) was added to the suiperinatte.…”

“…The role of hCG in the regulation of human fetal testes is of extreme interest in light of the hCGstimulated testosterone production and the highaffinity binding of the hormone found in this tissue (3). Unfortunately the minute size of the fetal gonad at this stage of gestation has precluded tissue explant study to date.3 The origin and role of the high concentration of hCG in ovary and thymus also remain obscure and await further investigation.…”

Extragonadal LH/hCG action—Not yet time to rewrite textbooks

“…The production of CG is confined to human, primate and equine placentas, whereas only pituitary LH is produced in rodents, including the mouse. hCG is essential for the maintenance of human pregnancy by stimulating progesterone production of corpus luteum gravidarum, and it also stimulates testosterone production of fetal Leydig cells (Huhtaniemi et al, 1977;Huhtaniemi and Pelliniemi, 1992;Huhtaniemi, 1994). In contrast to humans, the mouse genome does not contain a gene encoding chorionic gonadotroin.…”

Histological development of human testicular cords from 70 to 90 days of gestation

“…Male phenotype is controlled by two testicular hormones, the anti-Mullerian hormone (AMH) secreted by fetal Sertoli cells which induces regression of the Mullerian ducts (Josso et al, 1993(Josso et al, , 1998, and testosterone produced by fetal Leydig cells which induces differentiation of the Wolffian ducts into male reproductive organs (Winter et al, 1977). It is known that secretion of the human chorionic gonadotrophin (hCG) achieves a maximum peak around 80 days of gestation (Kaplan et al, 1976;Huhtaniemi et al, 1977;Mulchaney et al, 1987), and testosterone production was starts around 50 days of gestation and declines slowly after 100 days (Huhtaniemi, 1989). However, little information about the histological maturation of the testicular cord around 80 days of gestation is available.…”