Neuroendocrine mechanisms by which selective Leydig cell castration unleashes increased pulsatile LH release

Johannes D Veldhuis, Alexander D. Zwart, Ali Iranmanesh

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

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-h mean serum luteinizing hormone (LH) concentrations. Mechanistically, the unleashing of amplified pulsatile LH release can be accounted for by any of three distinct models of deconvolution-estimated gonadotropin secretion, all of which are marked by a nearly twofold 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analysis) rhythmicity of serum LH concentrations is not disturbed when androgenic negative-feedback signaling is withdrawn abruptly, but the apparent process randomness of LH release increases, as quantified by higher approximate entropy values.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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume272
Issue number2 41-2
StatePublished - 1997
Externally publishedYes

Fingerprint

Leydig Cells
Castration
Luteinizing Hormone
Ketoconazole
Entropy
Enzyme Inhibitors
Periodicity
Serum
Gonadotropins
Androgens
Half-Life
Pharmacology

Keywords

  • andregen
  • deconvolution
  • feedback
  • gonadotropin
  • human
  • ketoconazole

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Neuroendocrine mechanisms by which selective Leydig cell castration unleashes increased pulsatile LH release. / Veldhuis, Johannes D; Zwart, Alexander D.; Iranmanesh, Ali.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 272, No. 2 41-2, 1997.

Research output: Contribution to journalArticle

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