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Departments of Cell Biology and Physiology (S.R., T.M.P.) and Medicine (S.J.W.), University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261; Duquesne University School of Health Sciences (C.R.P.), Pittsburgh, Pennsylvania 15282; and the Medical Research Council Reproductive Biology Unit, University of Edinburgh (A.S.M.), Edinburgh, United Kingdom EH3 9EW
Address all correspondence and requests for reprints to: Dr. Tony M. Plant, Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine, S330 Biomedical Science Tower, Pittsburgh, Pennsylvania 15261.
In higher primates, FSH secretion appears to be regulated by a control
system consistent with that described by the classical inhibin
hypothesis. The purpose of the present experiment was to examine the
time course of inhibin’s action to suppress FSH secretion in the
intact adult male rhesus monkey. To this end, five adult males
implanted with indwelling venous catheters and exhibiting typical
episodic patterns of LH and testosterone (T) secretion received a 4-day
iv infusion of recombinant human (rh) inhibin A (832 ng/h·kg)
followed, after a 4-week interval, by vehicle infusion of similar
duration. Changes in circulating FSH concentrations during the inhibin
and vehicle infusions were determined using a sensitive homologous
macaque RIA, whereas enzyme-linked immunosorbent assays were employed
to track inhibin A, inhibin B, and inhibin pro-
-C levels during the
experiment. Normal pulsatile activity in the
hypothalamic-pituitary-Leydig cell axis was confirmed by monitoring
changes in circulating concentrations of LH and T in 12-h windows of
sequential blood collection (1200–2400 h; every 20 min) before,
during, and after the rh inhibin A and vehicle infusions. Although
infusion of rh inhibin A, which led to a 12 ng/ml square wave increment
in circulating levels of this inhibin dimer, produced a marked decline
in circulating FSH concentrations, significant suppression of the
secretion of this gonadotropin was not manifest until 54 h after
initiation of the infusion. Despite the marked decline in FSH secretion
during the last 24 h of the 4-day infusion of recombinant hormone,
circulating inhibin B and pro--C concentrations were maintained at
preinfusion control levels (1 ng/ml).
The finding that imposition of an exaggerated circulating inhibin signal led to suppression of FSH secretion in the male monkey only after 2 days of exposure to the hormone indicates that in this species the feedback action of testicular inhibin on FSH secretion is heavily lagged. Moreover, as the decrease in FSH did not lead to changes in native inhibin secretion, it seems reasonable to propose that the FSH-inhibin feedback loop that governs testicular function in higher primates operates with considerable hysteresis at both the pituitary and gonadal levels. The failure of dramatically elevated inhibin A levels to influence the pulsatile secretion of LH in the monkey reinforces the idea that in this species the pituitary action of testicular inhibin is specific for FSH and does not involve modulation of GnRH receptor levels.
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