title: Effect of progesterone withdrawal on hypothalamic mechanisms related to prolactin release in late pregnant rats.
abstract: OBJECTIVE
  Progesterone (P(4)) fall provoked by spontaneous or prostaglandin F2α (PGF2α)-induced luteolysis in late pregnant rats triggers a prolactin (PRL) surge 12-24 h later.
  
  
  METHODS
  To investigate the hypothalamic mechanism mediating this response, we determined expression of tyrosine hydroxylase (TH), PRL receptors (long form, PRLR(long)), estrogen-α (ERα) and ERβ, P(4) (PR) A and B receptors, and STAT5a, STAT5b, suppressors of cytokine signaling 1 (SOCS1), SOCS3 and CIS at mRNA (by semiquantitative and real-time RT-PCR) and protein (by Western blot only for TH, ERα and PRs) levels, and dopamine and DOPAC (by high-performance liquid chromatography) contents in the mediobasal hypothalamus (MBH) 24 h after luteolysis induced by a PGF2α analogue (cloprostenol, 25 μg/rat s.c. at 8 and 12 h on day 19 of pregnancy).
  
  
  RESULTS
  PGF2α treatment decreased circulating P(4) and estradiol and increased PRL and the estradiol/P(4) ratio. MBH DOPAC and DOPAC/dopamine ratio fell, indicating decreased dopaminergic transmission. PRLR(long), PRB and ERα mRNA increased. ERα and PR proteins were not modified. However, TH protein and mRNA did not change. PRA, the small PR isoform, was much more abundant than PRB, the isoform considered to mediate P(4) genomic actions. STAT5a, SOCS1 and SOCS3 mRNA were also increased.
  
  
  CONCLUSIONS
  The P(4) fall induced by PGF2α treatment induces PRL release through diminution in MBH dopaminergic transmission without change in TH expression. The increased PRLR along with elevated circulating PRL may be responsible for maintaining high TH expression through activation of short-loop feedback mechanisms, counteracting the effect of the fall in circulating P(4). In parallel, SOCS expression contributes to limit PRL signaling.
authors.affiliation: Laboratorio de Reproducción y Lactancia, IMBECU, CRICYT-CONICET, Mendoza, Argentina. mbonafede@mendoza-conicet.gov.ar
authors.forename: Melisa M
authors.initials: MM
authors.lastname: Bonafede
authors.forename: Susana R
authors.initials: SR
authors.lastname: Valdez
authors.forename: Fiorella Campo Verde
authors.initials: FC
authors.lastname: Arboccó
authors.forename: Gisela E
authors.initials: GE
authors.lastname: Pennacchio
authors.forename: Marta
authors.initials: M
authors.lastname: Soaje
authors.forename: Graciela A
authors.initials: GA
authors.lastname: Jahn
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002851:Chromatography, High Pressure Liquid; D015237:Dinoprost / Q000378:metabolism; D004298:Dopamine / Q000502:physiology; D004958:Estradiol / Q000097:blood; D005260:Female; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D008186:Luteolytic Agents / Q000494:pharmacology; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D011374:Progesterone / Q000097:blood / Q000494:pharmacology*; D011388:Prolactin / Q000378:metabolism*; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis
chemical_list: D008186:Luteolytic Agents; D015102:3,4-Dihydroxyphenylacetic Acid; D011374:Progesterone; D004958:Estradiol; D012313:RNA; D011388:Prolactin; D015237:Dinoprost; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine