Corticotropin-Releasing Factor (CRF) Agonists Stimulate Testosterone Production in Mouse Leydig Cells through CRF Receptor-11
The influence of CRF on testosterone production in primary mouse Leydig cell cultures was studied, and the type of CRF receptor (CRF-R) involved in this activity was determined. CRF directly stimulated testosterone production in mouse Leydig cells, but did not influence the maximum human (h)CG-induc...
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Published in | Endocrinology (Philadelphia) Vol. 139; no. 2; pp. 651 - 658 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Endocrine Society
01.02.1998
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Online Access | Get full text |
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Summary: | The influence of CRF on testosterone production in primary mouse Leydig
cell cultures was studied, and the type of CRF receptor (CRF-R)
involved in this activity was determined. CRF directly stimulated
testosterone production in mouse Leydig cells, but did not influence
the maximum human (h)CG-induced testosterone production. The effect was
time- and dose-dependent, saturable with an EC50 of 2.84
nm for hCRF, antagonized by the CRF antagonist α-helical
CRF9–41, and accompanied by intracellular cAMP elevation. The rank
order of potency of the natural CRF agonists, hCRF, ovine CRF,
sauvagine, and urotensin, corresponded to that of their activities on
CRF-R1 in rat pituitary cells and also to that reported for this
receptor, but not for CRF-R2, when transfected into various cell lines.
Furthermore, the difference in response of mouse Leydig cells to[
11-d-Thr,12-d-Phe]- and[
13-d-His,14-d-Leu]-ovine CRF corresponded to
that measured when COS cells expressing CRF-R1 were activated, but was
considerably smaller than that observed for activation of COS cells
expressing CRF-R2α or -R2β. The messenger RNA encoding the mouse
CRF-R1 was detected by RT-PCR in mouse Leydig cell preparations. In
contrast to mouse Leydig cells, CRF agonists had no influence on the
basal testosterone and cAMP production by rat Leydig cells, nor did the
agonists or antagonist change the hCG-stimulated testosterone and cAMP
production by these cells. It is concluded that mouse Leydig cells
express CRF-R1, mediating elevation of testosterone production by CRF
agonists through cAMP. Because potencies of CRF agonists in activating
mouse Leydig cells were more than 10-fold lower compared with their
potencies in stimulating rat pituitary cells, it is suggested that the
coupling of the CRF-R1 to intracellular signaling in Leydig cells is
different from that in corticotropic pituitary cells, at least in
quantitative terms. |
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ISSN: | 0013-7227 1945-7170 |
DOI: | 10.1210/endo.139.2.5754 |