Neuroendocrine mechanisms by which selective leydig-cell castration
unleashes increased pulsatile lh release.
Veldhuis, Johannes D., Alexander D. Zwart, Ali Iranmanesh.
Division of Endocrinology, Department of Internal Medicine,
University of Virginia Health Sciences Center, National Science
Foundation Center for Biological Timing, Charlottesville, Virginia
22908
APStracts 3:0307R, 1996.
A novel pharmacological model of acute reversible Leydig-cell
"castration" induced by a steroidogenic enzyme inhibitor,
ketoconazole, achieves marked hypoandrogenemia in healthy men with an
attendant 2.5-fold increase in 24-hour mean serum LH concentrations.
Mechanistically, the unleashing of amplified pulsatile LH release can
be accounted for by either of 3 distinct models of deconvolution
-estimated gonadotropin secretion, all of which are marked by a nearly
2-fold acceleration in LH secretory burst frequency. In addition, the
models variously also predict concomitant prolongation of the
endogenous LH half-life, an augmented LH secretory burst mass and
duration, and/or the emergence of significant basal LH secretion. The
nyctohemeral (cosinor analysis) rhythmicity of serum LH
concentrations is not disturbed when androgenic negative-feedback
signaling is withdrawn abruptly, but the apparent process randomness
of LH release increases, as quantified by higher approximate entropy
values. Thus, we conclude that an intact (closed-loop) androgen
-mediated negative-feedback network in the adult human male is
required to sustain low-frequency pulsatile LH release in a
quantifiably orderly manner.
Received 29 April 1996; accepted in final form 24 July 1996.
APS Manuscript Number R238-6.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 29 August 1996