GATA augments GNRH-mediated increases in Adcyap1 gene expression in pituitary gonadotrope cells

Abstract

Pituitary adenylate cyclase-activating polypeptide 1 (PACAP or ADCYAP1) regulates gonadotropin biosynthesis and secretion, both alone and in conjunction with gonadotropin-releasing hormone (GnRH). Initially identified as a hypothalamic-releasing factor, ADCYAP1 subsequently has been identified in pituitary gonadotropes, suggesting it may act as an autocrine-paracrine factor in this tissue. GnRH has been shown to increase pituitary Adcyap1 gene expression though the interaction of CREB and jun/fos with CRE/AP-1 cis-elements in the proximal promoter. For the current studies, we were interested in identifying additional transcription factors and cognate cis-elements which regulate Adcyap1 gene promoter activity and chose to focus on the GATA family of transcription factors known to be critical for both pituitary cell differentiation and gonadotropin subunit expression. By transient transfection and EMSA analysis, we demonstrate that GATA2 and GATA4 stimulate Adcyap1 promoter activity via a GATA cis-element located at position −191 in the rat Adcyap1 gene promoter. Furthermore, we show that addition of GATA2 or GATA4 significantly augments GnRH-mediated stimulation of Adcyap1 gene promoter activity in the gonadotrope LβT2 cell line. Conversely, blunting GATA expression with specific siRNA inhibits the ability of GnRH to stimulate ADCYAP1 mRNA levels in these cells. These data demonstrate a complex interaction between GnRH and GATA on ADCYAP1 expression, providing important new insights into the regulation of gonadotrope function.

An embryonic atrazine exposure results in reproductive dysfunction in adult zebrafish and morphological alterations in their offspring

“…The observed increase in ADCYAP1 expression in ovary tissue corresponds to the observed increase in P4 levels. Additionally, our previous study examining the effects of a developmental atrazine exposure on female brain tissue also revealed an alteration in ADCY upon transcriptomic analysis 33 as it works synergistically with GnRH, therefore playing a role in the release of LH and FSH 62 . All three are needed for proper reproductive function and each is shown to be decreased by atrazine exposure 8 27 40 .…”

“…An additional gene altered in ovarian tissue was the neuropeptide adenylate cyclase-activating peptide 1 ( ADCYAP1 ) which regulates gonadotropin gene expression. ADCYAP1 has widespread distribution and function which includes expression in the central and peripheral nervous system, adrenal glands, placenta, ovaries, and testes 62 . Estradiol and P4 stimulate the expression of ADCYAP1 in the hypothalamus and ovary 63 64 65 66 .…”

Post-partum anoestrus in tropical beef cattle: A systems approach combining gene expression and genome-wide association results

“…However, we detected the differential gene expression of ADCYAP1. Similarly to GnRH, the pituitary adenylate cyclase-activating polypeptide encoded by ADCYAP1 is also is secreted by hypothalamic neurons into the hypophyseal-pituitary portal vasculature and regulates gonadotropin gene expression (Thomas et al, 2013). It is tempting to speculate that in the beef cows studied here, differential expression of ADCYAP1during the post-partum period is an important and so far overlooked driver of increased ovarian follicular activity and ovulation.…”

Cloning and Expression Analysis of GATA1 gene in Carassius auratus red var.

“…used in the experiment has been sexually mature, so the GATA1 gene is most expressed in the testes in all tissues and organs. The GATA transcription factor family is essential for pituitary cell differentiation and gonadotropin subunit expression [27]. GATA1 inhibits the formation of rat cortical neurons, and overexpression of GATA1 in the hippocampus can cause depressive behavior in rats [28].…”