title: Facilitation or inhibition of the estradiol-induced gonadotropin surge in the immature rat by progesterone: regulation of GnRH and LH messenger RNAs and activation of GnRH neurons.
abstract: We have developed and extensively characterized immature female rat models to demonstrate inhibition or facilitation of the estradiol (E2)-induced gonadotropin surge by progesterone (P). We show here that the surge of free alpha-subunit is regulated similarly by P in these models. To investigate the possibility that P alters the biosynthesis of GnRH and/or LH, we measured levels of LH subunit mRNAs by Northern blot hybridization and GnRH mRNA by a solution hybridization-RNase protection assay. In the P inhibition model, alpha-subunit mRNA was significantly decreased when P was administered together with E2 for 32 or 48 h, and LHbeta, at 29 h. In the facilitation model, neither alpha-subunit nor LHbeta mRNA increased with premature and enhanced release of LH and free alpha-subunit. Levels of GnRH mRNA in E2-treated rats were significantly higher on the afternoon of the LH surge than on that or the following morning. There was no effect of P on GnRH mRNA levels, however, before, during, or after the LH surge in either paradigm. The time course of activation of GnRH neurons in P-facilitated rats was determined by double-label immunocytochemistry for GnRH and cFos. When serum LH concentrations were basal there was no expression of cFos in GnRH neurons. LH secretion in P-facilitated rats was initiated at 14.00 h and remained elevated until at least 19.00 h. During this time 63-78% of GnRH neurons were cFos positive. Both serum LH concentrations and the percentage of cFos-activated GnRH neurons were significantly lower in control rats treated with E2 alone than in those treated also with P.
  
  
  CONCLUSIONS
  1) suppression of LH and free alpha-subunit secretion by P can be accounted for at least partly by suppression of alpha-subunit mRNA levels; 2) P facilitation is not associated with changes in LH subunit or GnRH mRNA levels; 3) the large proportion of cFos-positive GnRH neurons in P-facilitated rats closely parallels increases in serum LH concentrations but is not accompanied by changes in GnRH mRNA levels. It is likely, therefore, that P acts in the facilitation model to trigger release of pre-existing GnRH stores by altering synthesis or activity of neuro-transmitters/neuropeptides involved in GnRH regulation and/or release of LH stores by altering, for example, pituitary responsiveness to GnRH (including self-priming) and components of the LH secretory apparatus. Similar possibilities may also obtain for the blockade of the gonadotropin surge in the inhibition model.
authors.affiliation: Department of Medicine and Cell Biology and Physiology, University of Pittsburgh School of Medicine, PA 15213, USA.
authors.forename: B
authors.initials: B
authors.lastname: Attardi
authors.forename: B
authors.initials: B
authors.lastname: Klatt
authors.forename: G E
authors.initials: GE
authors.lastname: Hoffman
authors.forename: M S
authors.initials: MS
authors.lastname: Smith
mesh_terms: D000818:Animals; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D016762:Genes, fos / Q000235:genetics; D015292:Glycoprotein Hormones, alpha Subunit / Q000235:genetics; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics*; D007700:Kinetics; D007986:Luteinizing Hormone / Q000235:genetics* / Q000378:metabolism*; D009474:Neurons / Q000502:physiology; D011374:Progesterone / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats
chemical_list: D015292:Glycoprotein Hormones, alpha Subunit; D012333:RNA, Messenger; D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone