Mammary gland-specific regulation of GNRH and GNRH-receptor gene expression is likely part of a local autoregulatory system in female vizcachas (Rodentia: Chinchillidae)

CORSO, MARÍA CLARA; CORTASA, SANTIAGO ANDRÉS; SCHMIDT, ALEJANDRO RAÚL; PROIETTO, SOFÍA; INSERRA, PABLO IGNACIO FELIPE; FERNÁNDEZ, MARINA OLGA; DI GIORGIO, NOELIA; LUX-LANTOS, VICTORIA; VITULLO, ALFREDO DANIEL; DORFMAN, VERÓNICA BERTA; HALPERIN, JULIA

GENERAL AND COMPARATIVE ENDOCRINOLOGY

ACADEMIC PRESS INC ELSEVIER SCIENCE

Año: 2020 vol. 296

0016-6480

n addition to key mammotrophic hormones such as the pituitary prolactin (PRL) and the ovarian steroids progesterone and estradiol, there are local factors thatmodulate the tissue dynamics of the mammary glands during pregnancy and lactation. By immunohistochemistry and RT-PCR, we found local transcription andtranslation of gonadotropin-releasing hormone (GNRH), GNRH receptor (GNRHR), PRL and PRL receptor (PRLR) in mammary glands of adult vizcachas duringpregnancy and lactation. Both GNRH and GNRHR showed a lag between protein expression and gene transcription throughout the gestational period: while thehighest transcription levels of these genes were recorded at early-pregnancy, the epithelial immunoexpressions of both showed their maximum during lactation. RIAresults corroborated the presence of GNRH in mammary glands at all the analyzed stages and confirmed the maximum amount of this peptide in the lactating group.Significant amounts of GNRH were detected in milk samples as well. Conversely, PRL and PRLR shared similar protein and gene expression profiles, all exhibitingmaximum values during lactation. GNRH peptide content in mammary glands of females with sulpiride-induced hyperprolactinemia (HP) was significantly lowerthan that of control females (CT). Although PRL mRNA levels remained unchanged, there was a marked increase in theα-lactalbumin (LALBA) transcription inmammary glands of HP- vs CT-females. These results suggest that after targeting mammary glands, PRL stimulates the expression of milk protein genes, but also,tempers the local expression of GNRH. Mammary gland-explants supplemented with a GNRH analogue (GN-explants) had no differences in terms of PRLR or LALBAtranscription levels compared to CT-explants, so the mammary PRLR signaling would not appear to be modulated by GNRH. Yet, mRNA expression levels of bothGNRH and the GNRHR-downstream factor, EGR1, were significantly higher in GN-explants compared to that of CT which would point to a GNRH-positive feedbackmechanism. In summary, the local coupled expression of GNRH, GNRHR and EGR1 in the mammary gland throughout pregnancy of vizcachas, the PRL-dependentmammary GNRH secretion as well as the GNRH positive feedback on its own transcription suggest an autocrine-paracrine regulatory mechanism and propose anactive role for GNRH in mammary gland tissue remodeling.