Effect of Progesterone Withdrawal on Hypothalamic Mechanisms Related to Prolactin Release in Late Pregnant Rats

BONAFEDE MM; VALDEZ SR; CAMPO VERDE ARBOCCÓ F; PENNACCHIO GE; SOAJE M; JAHN GA

NEUROENDOCRINOLOGY

KARGER

Lugar: Basel; Año: 2011 p. 148 - 157

0028-3835

Abstract Background/Aims: Progesterone (P 4 ) fall provoked by spon- taneous or prostaglandin F2 (PGF2 )-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 tyro- sine hydroxylase (TH), PRL receptors (long form, PRLR long ), estrogen- (ER ) and ER , 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, ER and PRs) levels, and dopamine and DOPAC (by high-performance liquid chromatography) contents in the mediobasal hypo- thalamus (MBH) 24 h after luteolysis induced by a PGF2 an- alogue (cloprostenol, 25 g/rat s.c. at 8 and 12 h on day 19 of pregnancy). Results: PGF2 treatment decreased circulating P 4 and estradiol and increased PRL and the estradiol/P 4 ratio. MBH DOPAC and DOPAC/dopamine ratio fell, indicating de- creased dopaminergic transmission. PRLR long , PRB and ER mRNA increased. ER 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. Conclusion: The P 4 fall induced by PGF2 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 main- taining 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 lim- it PRL signaling.