Abstract
Secretogranin II (SgII) is an acidic 86-kD protein which is synthesized by most neuroendocrine cells but occurs in greatest abundance in the anterior pituitary gland where it is localized primarily in gonadotrophs. In the present studies, we investigated the regulation of SgII mRNA expression in the anterior pituitary gland by estrogens and gonadotropin-releasing hormone (GnRH) and compared the results to luteinizing hormone beta-subunit (LH beta) mRNA expression. Molecular cloning and nucleotide sequence analysis of a rat pituitary SgII cDNA revealed a derived amino acid sequence identical with that previously reported for the rat adrenal. Not previously reported were five putative nuclear localization signals, four of which coincided with dibasic residues previously thought to serve as proteolytic cleavage sites. In Northern blots, SgII mRNA was found in high abundance in the anterior pituitary gland, in moderate abundance in the brain and adrenal, and in low abundance in the ovary and testis. Measurements of pituitary SgII mRNA during the rat 4-day estrous cycle revealed an inverse relationship with LH beta mRNA: SgII mRNA decreased, whereas LH beta mRNA increased as the cycle progressed. Increases in pituitary SgII mRNA and LH beta mRNA levels occurred after ovariectomy, and decreases occurred after estrogen treatment of such animals. Likewise, pituitary SgII mRNA and LH beta mRNA levels decreased after treatment of ovariectomized animals with a GnRH antagonist. In contrast, ovariectomy significantly decreased SgII mRNA levels in the hypothalamus, and estrogen treatment increased its levels. Our studies reveal that ovarian estrogens and hypothalamic GnRH exert similar effects on SgII mRNA and LH beta mRNA expression in the pituitary. However, since their expression is inverse during the rat estrous cycle, other unidentified regulatory factors with differential effects on their expression may intervene in the regulation of SgII and LH beta mRNA levels.
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