The role of estrogen-dependent progesterone receptor in protein kinase C-mediated LH secretion and GnRH self-priming in rat anterior pituitary glands.
The aim of the present study was to explore the involvement of pituitary progesterone receptor (PR) in PKC-mediated LH secretion and LHRH self-priming and the role of the estrogen (E) environment. Eight randomly selected hemipituitaries from adult female rats in proestrus or from 2 weeks ovariectomized (OVX) rats were incubated, in the absence of progesterone (P), over 3 h in Dulbecco's modified Eagle's medium (DMEM). In the first experiment, hemipituitaries were incubated continuously with: medium alone, GnRH (10 nM), the PKC stimulator PMA (100 nM), the PKC inhibitor staurosporine (100 nM), the antiprogestin at the receptor RU486 (10 nM), LHRH+staurosporine, GnRH+RU486 or PMA+RU486. In the second experiment, hemipituitaries were incubated, one h apart, with GnRH to determine the GnRH self-priming and this was compared with the priming effect of PMA. Also, the effect of staurosporine and RU486 during the induction period (1st h) on GnRH and PMA priming was evaluated. Medium was aspirated at the end of each h to determine LH accumulation and to evaluate GnRH self-priming. Both GnRH and PMA stimulated LH secretion. Staurosporine and RU486 reduced basal and GnRH-stimulated LH secretion, and RU486 reduced PMA-stimulated LH secretion from proestrus pituitaries. The stimulating effect of GnRH and PMA on LH secretion and the inhibitory action of staurosporine and RU486 on basal or stimulated LH secretion were significantly reduced in OVX-rats. Both GnRH and PMA induced GnRH priming. Staurosporine during the induction h reduced GnRH self-priming while RU486 reduced both GnRH self-potentiation and PMA priming. The magnitude of these inhibitory effects was blunted in OVX-rats. These results showed that PKC signaling pathway in the gonadotrope mediates, at least in part, basal and GnRH-stimulated LH secretion and GnRH self-priming. Also, the results are suggestive of an interaction of PKC signaling pathway with E-dependent PR in a ligand-independent activation manner in the gonadotrope.
Aguilar
R
R
Department of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain.
Bellido
C
C
Sánchez-Criado
J E
JE
D000818:Animals; D004334:Drug Administration Schedule; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage*; D006727:Hormone Antagonists / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000378:metabolism*; D015735:Mifepristone / Q000494:pharmacology; D010052:Ovariectomy; D010903:Pituitary Gland, Anterior / Q000502:physiology*; D011374:Progesterone / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011980:Receptors, Progesterone / Q000502:physiology*; D019311:Staurosporine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D004967:Estrogens; D006727:Hormone Antagonists; D011980:Receptors, Progesterone; D015735:Mifepristone; D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone; D007986:Luteinizing Hormone; D011493:Protein Kinase C; D019311:Staurosporine