Understanding the regulation of pituitary progesterone receptor expression and phosphorylation.
Administration of human FSH (hFSH) during the diestrus phase in cyclic rats is followed by a reduction in the preovulatory LH surge. This inhibitory action of FSH involves a decrease in the stimulatory effect of gonadotrope progesterone receptor (PR) activation, in a ligand-dependent (progesterone) and -independent (GNRH) manner. PR activation and action are mandatory for LH surge, and are dependent on the phosphorylation of serine (Ser) residues. Together with this post-translational modification, PR is marked for downregulation by proteasome machinery. These experiments used the western blotting technique to measure pituitary expression of PR-A and PR-B isoforms and phosphorylation levels of Ser294 and Ser400 PR-B in rats bearing i) hFSH treatment or ii) PR downregulation. Treatment with hFSH reduced LH secretion and increased that of estradiol in proestrus afternoon. hFSH injections, without altering PR-A and PR-B content or ratio, caused a reduction in phosphorylation of Ser294 and Ser400 but only when pituitaries were previously challenged with progesterone or GNRH for 2 h. However, while pSer294 levels increased after 2 h of pituitary incubation with progesterone or GNRH, those of pSer400 were not modified by these in vitro treatments. Finally, progesterone had a biphasic effect: in 2-h incubations increased pituitary PR-A and PR-B content, but after 8 h caused downregulation and altered PR-A:PR-B ratio. The results provide a potential mechanism through which LH levels are decreased by hFSH administration and better understanding of the control of PR expression and phosphorylation in rat pituitaries.
Department of Cell BiologyPhysiology and Immunology, University of Córdoba, 14004 Córdoba, Spain anagordonbc@gmail.com.
Ana
A
Gordon
Department of Cell BiologyPhysiology and Immunology, University of Córdoba, 14004 Córdoba, Spain.
José C
JC
Garrido-Gracia
Department of Cell BiologyPhysiology and Immunology, University of Córdoba, 14004 Córdoba, Spain.
Rafaela
R
Aguilar
Department of Cell BiologyPhysiology and Immunology, University of Córdoba, 14004 Córdoba, Spain.
José E
JE
Sánchez-Criado
D000818:Animals; D004958:Estradiol / Q000378:metabolism; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000378:metabolism; D010766:Phosphorylation; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D011374:Progesterone / Q000378:metabolism / Q000494:pharmacology; D011499:Protein Processing, Post-Translational / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism*
D011980:Receptors, Progesterone; D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone