TY - JOUR

T1 - Central activin administration modulates corticotropin-releasing hormone and adrenocorticotropin secretion

AU - Plotsky, Paul M.

AU - Kjær, Andreas

AU - Sutton, Steve W.

AU - Sawchenko, Paul E.

AU - Vale, Wylie

PY - 1991/5/1

Y1 - 1991/5/1

N2 - A broad and diffuse neuronal network conveys information reflecting the state of the internal and external environment to the neurosecretory hypothalamus. Recently, we identified an inhibin-βA- (IβA) immunoreactive terminal field within the CRF-rich portion of the dorsomedial paraventricular nucleus which originates from a cell group in the commissural portion of the nucleus of the solitary tract (NTS). The NTS receives baroreceptor input, somatosensory input via the spino- solitary tract, and sensory information from the oral, thoracic, and abdominal cavities and, thus, is positioned to serve as a primary relay for visceral sensory inputs to neurons critical to the function of the hypothalamic-pituitary-adrenal (HPA) axis. Although these NTS cells contain multiple putative transmitters, we present evidence that activin, an inhibin-/SA dimer, plays a modulatory role in HPA axis function via facilitation of CRF release. First, intraventricular injection of activin-A (0-3 nmol), but not the related inhibin heterodimer, evoked dose-related 1.7- to 2.8-fold elevations of circulating ACTH levels in male rats. Second, analysis of hypophysial-portal plasma after bilateral paraventricular nucleus microinfusion of activin-A revealed a dose-related facilitation of CRF secretion up to 4-fold above preinjection levels which was unaccompanied by changes in arginine vasopressin levels. Finally, activin-A also enhanced CRF secretion from neonatal hypothalamic cells in primary culture with an EC50 dose of approximately 0.25 nM. Overall, these observations provide evidence of both an anatomical and a pharmacological substrate for activin-mediated central modu-lation of HPA axis function.

AB - A broad and diffuse neuronal network conveys information reflecting the state of the internal and external environment to the neurosecretory hypothalamus. Recently, we identified an inhibin-βA- (IβA) immunoreactive terminal field within the CRF-rich portion of the dorsomedial paraventricular nucleus which originates from a cell group in the commissural portion of the nucleus of the solitary tract (NTS). The NTS receives baroreceptor input, somatosensory input via the spino- solitary tract, and sensory information from the oral, thoracic, and abdominal cavities and, thus, is positioned to serve as a primary relay for visceral sensory inputs to neurons critical to the function of the hypothalamic-pituitary-adrenal (HPA) axis. Although these NTS cells contain multiple putative transmitters, we present evidence that activin, an inhibin-/SA dimer, plays a modulatory role in HPA axis function via facilitation of CRF release. First, intraventricular injection of activin-A (0-3 nmol), but not the related inhibin heterodimer, evoked dose-related 1.7- to 2.8-fold elevations of circulating ACTH levels in male rats. Second, analysis of hypophysial-portal plasma after bilateral paraventricular nucleus microinfusion of activin-A revealed a dose-related facilitation of CRF secretion up to 4-fold above preinjection levels which was unaccompanied by changes in arginine vasopressin levels. Finally, activin-A also enhanced CRF secretion from neonatal hypothalamic cells in primary culture with an EC50 dose of approximately 0.25 nM. Overall, these observations provide evidence of both an anatomical and a pharmacological substrate for activin-mediated central modu-lation of HPA axis function.

UR - http://www.scopus.com/inward/record.url?scp=0025828374&partnerID=8YFLogxK

U2 - 10.1210/endo-128-5-2520

DO - 10.1210/endo-128-5-2520

M3 - Journal article

C2 - 1850353

AN - SCOPUS:0025828374

VL - 128

SP - 2520

EP - 2525

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0013-7227

IS - 5

ER -