Corticotropin-Releasing Factor Stimulates Accumulation of Adenosine 3′,5′-Monophosphate in Rat Pituitary Corticotrophs

Abstract

The presence of synthetic ovine corticotropin-releasing factor leads to a rapid and marked stimulation of adenosine 3', 5'-monophosphate accumulation in an enriched population of rat pituitary corticotrophs in primary culture. The increase, observed as early as 60 seconds after the addition of corticotropin-releasing factor, suggests that changes in the intracellular concentration of the cyclic nucleotide coincide with or precede the secretion of adrenocorticotropic hormone in response to corticotropin-releasing factor.

Glucocorticoids rapidly inhibit oxytocin-stimulated adrenocorticotropin release from rat anterior pituitary cells, without modifying intracellular calcium transients.

“…Experimental evidence reported by different groups, that is secretion studies in the presence or absence of extracellular calcium or direct measurements of calcium transients in corticotropes exposed to OT or A VP (6,9,35,36), emphasizes the involvement of intracellular calcium stores during ACTH release. On the other hand, CRF causes influx of extracellular calcium through calcium channels, and these influxes are secondary to CRF-stimulated cAMP production (8,37,38). It has been proposed that calcium channels in a variety of cells are activated by cAMP (39,40).…”

“…In all cells analyzed, the OT-induced intracellular calcium transients were not substantially different when the steroids were present. (8,37,38). It has been proposed that calcium channels in a variety of cells are activated by CAMP (39,40).…”

Effect of synthetic ovine corticotropin-releasing factor. Dose response of plasma adrenocorticotropin and cortisol.

“…It has since been synthesized (5, 7) and shown to be active in vitro (5) and in vivo (8). The action of CRF, which apparently involves generation of intracellular adenosine 3',5'-monophosphate (24), can be inhibited by prior exposure to glucocorticoids, such as dexamethasone (8).…”

Corticotropin-releasing hormone excites adrenocorticotropin-secreting human pituitary adenoma cells by activating a nonselective cation current.

“…ACTH-secreting pituitary adenomas were obtained with informed consent from three patients operated for ACTH-secreting pituitary adenoma by transsphenoidal surgery (patients [1][2][3]. The use of surgically removed human pituitary tissues obtained during surgery as experimental materials is permitted by the Investigation Committee of Hypothalamo-Pituitary Diseases, The Ministry of Health and Welfare of Japan, and The Ethical Committee of University of Tokyo School of Medicine (Tokyo, Japan).…”

“…The mechanism of CRH-induced ACTH secretion has been investigated using rat corticotrophs and AtT-20 cells, an ACTH-secreting mouse pituitary cell line, and ACTH-secreting human pituitary adenoma cells. CRH stimulates ACTH secretion through the activation of adenylyl cyclase (3,4) and through the increase in intracellular Ca 2 ϩ concentration ([Ca…”