Prolactin Is a Strong Candidate for the Regulation of Luteal Steroidogenesis in Vizcachas (Lagostomus maximus).

Prolactin (PRL) is essential for the maintenance of the corpora lutea and the production of progesterone (P4) during gestation of mice and rats, which makes it a key factor for their successful reproduction. Unlike these rodents and the vast majority of mammals, female vizcachas (Lagostomus maximus) have a peculiar reproductive biology characterized by an ovulatory event during pregnancy that generates secondary corpora lutea with a consequent increment of the circulating P4. We found that, although the expression of pituitary PRL increased steadily during pregnancy, its ovarian receptor (PRLR) reached its maximum in midpregnancy and drastically decreased at term pregnancy. The luteinizing hormone receptor (LHR) exhibited a similar profile than PRLR. Maximum P4 and LH blood levels were recorded at midpregnancy as well. Remarkably, the P4-sinthesizing enzyme 3ß-HSD accompanied the expression pattern of PRLR/LHR throughout gestation. Instead, the luteolytic enzyme 20α-HSD showed low expression at early and midpregnancy, but reached its maximum at the end of gestation, when PRLR/LHR/3ß-HSD expressions and circulating P4 were minimal. In conclusion, both the PRLR and LHR expressions in the ovary would define the success of gestation in vizcachas by modulating the levels of 20α-HSD and 3ß-HSD, which ultimately determine the level of serum P4 throughout gestation.

Effects on mouse uterus of three antitumoral drugs acting upon estrogen and progesterone receptors directly and through other transduction pathways.

Three antitumoral drugs, tamoxifen (Tam), medroxyprogesterone acetate (MPA), and 8-Cl-cyclic AMP (8Cl), were administered separately and in combination to normal adult mice in order to record their effects on uterus weight, on estrous cycle, and on two estrogen receptor (ER) and progesterone receptor (PgR) parameters, namely content and nucleo-cytoplasm distribution. Tam decreased uterus weight (49%) and total ER content (118+/-6 vs 328+/-20 fmol/mg protein in controls) but increased total PgR (1183+/-230 vs 743+/-52 fmol/mg protein in controls) and nuclear retention of ER and PgR. MPA down-regulated PgR content and increased uterus weight (36%), but failed to modify ER and PgR nuclear retention. The only parameter changed by 8Cl was nucleo-cytoplasm PgR distribution. Tam + MPA association produced the same results as Tam alone for ER and PgR nuclear retention, but receptor content was not significantly different from that of controls. Both drugs, administered separately, had opposite effects on PgR content; when both were acting concurrently, an algebraic addition of effects was observed, as if both transcription circuits were triggered independently. Remaining Tam effects, not modified by a combination with MPA, indicated the predominance of Tam on the corresponding parameters. When Tam and 8Cl were administered together, 8Cl counteracted the effect of Tam only on PgR content. When associated with MPA, 8Cl changed the effects of MPA on ER and PgR nuclear retention, whereas on receptor content, only that of ER was increased (502+/-47 vs 328+/-20 fmol/mg protein in controls). These crossed effects indicate that interrelations between different transduction pathways can affect certain functional circuits while sparing others. The possibility of acting pharmacologically upon different transcription pathways represents a novel approach to modify drug effects directed to specific transduction targets through cross-talk between their components.