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Population Council (M.K., P.L.M) and The Rockefeller University (P.L.M.), New York, New York 10021
Address all correspondence and requests for reprints to: Dr. Patricia L. Morris, Center for Biomedical Research, Population Council and The Rockefeller University, 1230 York Avenue, New York, New York 10021. E-mail: p-morris{at}popcbr.rockefeller.edu
Gonadal development and differentiation is dependent in part on GH, as
GH deficiency has been implicated as a cause of lowered fertility and
spermatogenic cessation in humans and some biological models. In this
study, we demonstrate that GH receptor messenger RNA (mRNA) is
preferentially expressed in progenitor Leydig cells (PLCs) isolated and
purified from 21-day-old rats. GH induces significant increases in the
levels of steroidogenic acute regulatory protein (StAR),
3ß-hydroxysteroid dehydrogenase (3ß-HSD) expression, and androgen
production in PLCs. Additionally, the cytokine interferon-
(IFN)
markedly inhibits GH-stimulated StAR mRNA and protein levels. When
cells are cultured with both GH and IFN, IFN decreases the
stimulating effect of GH on androgen production. Treatment of PLCs with
cycloheximide does not prevent the GH-induced StAR mRNA, indicating
that GH induction of StAR transcripts does not require de
novo protein synthesis. In contrast, the induction of 3ß-HSD
mRNA by GH is altered by cycloheximide treatment. H7, a
serine/threonine kinase inhibitor, completely abrogates the increases
in StAR mRNA by GH, whereas the tyrosine kinase inhibitor genistein
does not. Moreover, GH further enhances StAR and 3ß-HSD mRNA
expression in isolated adult rat Leydig cells despite their increased
basal expression subsequent to maturational acquisition of these
steroidogenic components. These data provide the first demonstration of
the direct effects of GH on testicular steroidogenesis during
progenitor Leydig cell differentiation.
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L. Walch, E. Clavarino, and P. L. Morris Prostaglandin (PG) FP and EP1 Receptors Mediate PGF2{alpha} and PGE2 Regulation of Interleukin-1{beta} Expression in Leydig Cell Progenitors Endocrinology, April 1, 2003; 144(4): 1284 - 1291. [Abstract] [Full Text] [PDF]
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L. Walch and P. L. Morris Cyclooxygenase 2 Pathway Mediates IL-1{beta} Regulation of IL-1{alpha}, -1{beta}, and IL-6 mRNA Levels in Leydig Cell Progenitors Endocrinology, September 1, 2002; 143(9): 3276 - 3283. [Abstract] [Full Text] [PDF]
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D. E. Keene, M. O. Suescun, M. G. Bostwick, V. Chandrashekar, A. Bartke, and J. J. Kopchick Puberty Is Delayed in Male Growth Hormone Receptor Gene--Disrupted Mice J Androl, September 1, 2002; 23(5): 661 - 668. [Abstract] [Full Text] [PDF]
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