Derivatization of progesterone to a neurally active steroid by pituitary neurointermediate lobe

Joshua A. Berman, T. J. Wu, James L. Roberts

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

The melanotrophs of the neurointermediate lobe and peptidergic terminals of the neural lobe are regulated by gamma-aminobutyric acid (GABA) via GABA- A receptors and therefore, may be important sites for the modulatory actions of neurally active steroids. These steroid compounds might be produced peripherally, synthesized de novo in the pituitary, or derivatized from circulating steroids, each pathway having different physiological implications. In the present study, we show that neurointermediate lobe tissue can derivatize progesterone to the neurally active steroid 3α- hydroxy-5α-pregnan-20-one. The neurointermediate lobe was found to be four times as active as anterior pituitary and mediobasal hypothalamus in conversion of progesterone to 3α-hydroxy-5α-pregnan-20-one; mediobasal hypothalamus was relatively more active in the production of the intermediate 5α-pregnan-3,20-dione. The identity of the compounds was confirmed by the method of serial isotopic dilution. We observed rates of synthesis in the neurointermediate lobe consistent with the production of physiologically relevant quantities of 3α-hydroxy-5α-pregnan-20-one from concentrations of progesterone which can occur naturally. In support of these findings, we demonstrate the presence of 3α-hydroxysteroid oxidoreductase in neurointermediate lobe by immunocytochemistry.

Original languageEnglish (US)
Pages (from-to)579-586
Number of pages8
JournalSteroids
Volume63
Issue number11
DOIs
StatePublished - Nov 1 1998
Externally publishedYes

Keywords

  • 3α hydroxy-5-α-pregnan-20-one neurosteroid pituitary
  • 3α hydroxysteroid oxidoreductase
  • Melanotroph
  • Neurointermediate lobe

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology
  • Pharmacology
  • Clinical Biochemistry
  • Organic Chemistry

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