Biological role of pituitary estrogen receptors ERalpha and ERbeta on progesterone receptor expression and action and on gonadotropin and prolactin secretion in the rat.
Estrogen (E) is a key regulator of the synthesis and secretion of pituitary reproductive hormones [luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin (PRL)]. Until recently, it was thought that all biological actions of E at the pituitary were manifested through a single E receptor (R). The pituitary, like many other reproductive tissues, expresses two isoforms of ER, alpha and beta, both activated by E. The relative contribution of alpha and beta forms in E regulatory actions is largely unknown. To this end, 2-week-old ovariectomized (OVX) rats were injected over 3 days with 25 microg estradiol benzoate (EB), 1.5 mg of propylpyrazole triol (PPT), a selective ERalpha agonist, 1.5 mg of the selective ERbeta agonist diarylpropionitrile (DPN) or a combination of PPT and DPN. Controls were injected with 0.2 ml oil. At 10:00 h on the day after treatment, trunk blood was collected to determine serum concentration of LH, FSH and PRL, and pituitaries were processed for RT-PCR analysis of total (A+B) progesterone receptor (PR) mRNA, immunocytochemistry of PR and incubation. Pituitaries from each of the five groups were incubated in DMEM, with or without 20 nM of the antiprogestin at the receptor ZK299, for 3 h with: 10(-8)M 17beta-estradiol, 10(-6)M PPT, 10(-6)M DPN, PPT+DPN or medium alone, respectively, to determine LH, FSH and PRL secretion, and, when challenged with two pulses of 15 min 1 h apart of 10(-8)M gonadotropin-releasing hormone (GnRH) (GnRH self-priming). EB, PPT and PPT+DPN treatments increased PR mRNA and the number and intensity of nuclei immunoreactive (IR) for PR in gonadotropes, and reduced the number of gonadectomy cells. Like E, PPT alone or in combination with DPN stimulated PRL secretion, increased basal and GnRH-stimulated LH and FSH secretion and induced GnRH self-priming in the absence of ZK299 in the incubation medium. DPN alone had only a significant E-like effect on gonadectomy cells and IR-PR, but not on GnRH self-priming. In addition, while DPN lacked an agonistic action on peripheral tissue and serum pituitary reproductive hormones concentration, EB, PPT and PPT+DPN induced similar uterine ballooning and vaginal cornification, and increased and decreased, respectively, serum concentrations of PRL and gonadotropins. Overall, these results indicate that most of these E actions on the pituitary are exerted through the ERalpha isoform. The finding that activation of ERbeta with its selective DPN agonist had an estrogenic effect on IR-PR nuclei, but not on GnRH self-priming, a characteristic ERalpha-mediated effect of E, suggests that the biological action of E at the pituitary may involve both isoforms of ER.
Sánchez-Criado
José E
JE
Department of Cell Biology, Physiology and Inmunology, University of Córdoba, Córdoba, Spain. fi1sacrj@uco.es
Martín De Las Mulas
Juana
J
Bellido
Carmina
C
Tena-Sempere
Manuel
M
Aguilar
Rafaela
R
Blanco
Alfonso
A
D000704:Analysis of Variance; D000818:Animals; D004347:Drug Interactions; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000502:physiology; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D005260:Female; D005640:Follicle Stimulating Hormone / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D006065:Gonadotropins, Pituitary / Q000235:genetics / Q000378:metabolism*; D008024:Ligands; D007986:Luteinizing Hormone / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D010052:Ovariectomy; D010636:Phenols; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D011388:Prolactin / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D011422:Propionates / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D011960:Receptors, Estrogen / Q000819:agonists / Q000502:physiology*; D011980:Receptors, Progesterone / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
C486182:2,3-bis(4-hydroxyphenyl)-propionitrile; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D006065:Gonadotropins, Pituitary; D008024:Ligands; D009570:Nitriles; D010636:Phenols; D011422:Propionates; D011720:Pyrazoles; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C486184:4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol; C074283:estradiol 3-benzoate; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D011388:Prolactin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone