Regulatory Effects of Estrogens on the Pituitary Content of Secretogranin II and Chromogranin A

Abstract

Modulation of pituitary content of secretogranin II and chromogranin A has been compared to that of luteinizing hormone (LH) in adult female rats following gonadectomy and subsequent estradiol therapy. Both proteins were quantified using two specific antisera, BS 487 and anti-CAP-14, respectively. Ovariectomy promoted an increase in the concentration of secretogranin II and chromogranin A, though to a lesser degree than that of LH. Moreover, intracellular processing of secretogranin II was significantly enhanced.Daily estradiol injection further increased pituitary secretogranin II and LH contents while that of chromogranin A was reduced to sham-operated control values. These data 1) demonstrate that both granins are differentially regulated through ovarian factors, and 2) confirm that regulation of secretogranin II production may be closely related to that of LH.Secretogranin I1 and chromogranin A are widespread constituents of secretory granules in neuroendocrine cells (1-3). Their function is still largely unknown though their participation in intracellular processes such as sorting or packaging of hormones (4) as well as in extracellular regulatory mechanisms on target cells ( 5 ) has been suggested and reported (6, 7). Any review concerning these proteins states that secretogranin I1 is highly abundant in the pituitary where it was first discovered, while the level of chromogranin A is lower. However, in a recent study, we could demonstrate that concentration of both proteins was high in the female rat pituitary during sexual maturation, and that concentration of chromogranin A fell markedly to low values in the adult pituitary while that of secretogranin I1 was highly sustained and clearly modulated during the estrous cycle (8).This observation prompted us to analyse the putative regulatory effects of gonadal steroids on the synthesis and storage of pituitary secretogranin 11 and chromogranin A. We have thus determined the effects of gonadectomy and subsequent estrogen therapy on the content of both proteins and compared these data with the modulation of pituitary LH production in the same conditions.In order to assess the efficiency of gonadectomy and that of subsequent estrogen therapy, uterine weight and serum LH concentration were determined in each individual. As reported in Table I , uterine weight was severely depressed 21 days following ovariectomy as compared to sham-operated controls, while it was restored after seven daily injections of estradiol. Simultaneously, circulating LH level was high in gonadectomized animals while the steroid hormone brought it back to low values. Pituitary secretogranin I1 was quantified following Western blotting using the previously characterized anti-rat secretogranin I1 antiserum BS 487 (9, 10) and densitometry of the main 8 7 K band. As depicted in Fig.

Sex‐Related Differences in Chromogranin A, Chromogranin B and Secretogranin II Gene Expression in Rat Pituitary

“…This result explains recent data by Anouar and Duval (26) who reported decreasing levels of chromogranin A in the pituitary during maturation of female rats. In addition, our studies are in agreement with a recent study (27) showing increased chromogranin A immunoreactivity in pituitaries of ovariectomized rats. Suppression of chromogranin A gene expression by circulating estrogen appears to be limited to anterior pituitary cells, as chromogranin A mRNA levels were not significantly altered in any other tissue investigated.…”