Positive regulation of proopiomelanocortin gene expression in corticotropes and melanotropes

N. Levin, J. L. Roberts

Research output: Contribution to journalReview article

44 Scopus citations

Abstract

The in vivo synthesis and secretion of proopiomelanocortin (POMC)-derived peptides from the pituitary are tightly controlled by a variety of hypothalamic neuroendocrine factors and by circulating glucocorticoids, which maintain appropriate serum concentrations and pituitary stores of adrenocorticotropic hormone (ACTH) and alpha melanocyte-stimulating hormone (α-MSH). The neuroendocrine factors which stimulate POMC-derived peptide secretion do so via several well-characterized intracellular pathways; intracellular mediators ('second messengers') of these pathways also modulate POMC gene expression. In this article, we have focused on the stimulation of POMC gene expression by factors affecting intracellular cyclic adenosine monophosphate (cAMP) content, regulators of phospholipid turnover, and intracellular Ca2+ fluxes. In all of the pituitary models discussed, cAMP stimulates POMC gene transcription. It is suggested that cAMP stimulates POMC gene expression by at least two mechanisms: activation of cAMP-dependent protein kinase A and increase of intracellular calcium ion levels via voltage-sensitive Ca2+ channels. Increased phospholipid turnover and direct activation of protein kinase C by phorbol esters do not exhibit consistent effects on POMC gene expression in the pituitary models discussed here and it is suggested that protein kinase C activation may affect pituitary POMC gene expression by a posttranscriptional mechanism. In light of this discussion, we have also considered the impact of adrenalectomy and acute stress of insulin-induced hypoglycemia, stimuli which activate secretion of hypothalamic ACTH-releasing factors, on in vivo pituitary POMC gene expression.

Original languageEnglish (US)
Pages (from-to)1-22
Number of pages22
JournalFrontiers in Neuroendocrinology
Volume12
Issue number1
StatePublished - Jan 1 1991
Externally publishedYes

ASJC Scopus subject areas

  • Endocrine and Autonomic Systems

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