Reproductive Endocrinology, Department of Obstetrics and Gynecology, Rambam Medical Center and the B. Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, 31096, Israel
Address for correspondence: Zeev Blumenfeld, Reproductive Endocrinology, Department of Obstetrics and Gynecology, Rambam Medical Center, The B. Rappaport Faculty of Medicine, Technion—Israel Institute of Technology, Haifa, 31096, Israel. Voice: 972-4-8542577; fax: 972-4-8542612.
bzeev{at}techunix.technion.ac.il
Background: Activin has been previously demonstrated to directly
stimulate the synthesis of gonadotropin-releasing hormone (GnRH)
receptors and to increase follicle-stimulating hormone (FSH)
secretion in nonhuman pituitary cell cultures (PCCs). Currently,
knowledge of the physiological role of these peptides in primates
is still far from complete. Moreover, several results in macaque
monkeys failed to support an unequivocal role for inhibin in
FSH suppression. Whereas the bioactivity of inhibin and activin
has been demonstrated in rat PCCs, no data exist on human pituitary
response to these peptides either
in vivo or
in vitro.
Methods:
We studied the secretion of FSH and luteinizing hormone (LH)
by dispersed human fetal pituitary cells from midtrimester abortions
in response to recombinant human (rh-) activin-A, inhibin-A,
and other secretagogues. After mechanical and enzymatic dispersion,
the human fetal pituitary cells were cultured on an extracellular
matrixlikematerial-coated 24-well plate. After 3 days' incubation
in serum-containing medium, the PCCs were washed and preincubated
for 90 min in serum-free medium and incubated with activin-A,
inhibin-A, TGF-ß, follistatin, sex steroids, and GnRH,
in quadruplicate.
Results: Activin-A was a potent secretagogue
for FSH secretion. GnRH (20 ng/ml) was more potent than rh-activin-A
for LH secretion. Nevertheless, a significant increase in LH
secretion into the medium was brought about by rh-activin-A.
Inhibin decreased FSH and LH secretion, but the LH response
to inhibin was less prominent than that of FSH. GnRH opposed
the inhibitory effect of inhibin on LH secretion. In dynamic,
short-term, repetitive exposure of fetal pituitary fragments
to rh-activin-A (superfusion), we could not receive a similar
increase in LH and FSH as in static incubations, as opposed
to a short GnRH exposure. In addition to their endocrine, paracrine,
and autocrine effects, and in addition to their role as possible
markers, the TGF-ß superfamily members may affect
embryogenesis and possibly immunomodulation of the embryo and
fetus. The role of activin and inhibin as intragonadal regulators
is hypothesized. The pro-
C inhibin precursor may act as an FSH
receptor antagonist.
Conclusions: Human fetal PCCs express the
previously reported physiologic responses to activin and inhibin
generated in nonhuman experiments on gonadotropin secretion
in vitro and may serve as a physiologic model for studying human
gonadotrope responses to the TGF-ß family of peptides.
