Dynorphin and the hypothalamo-pituitary-adrenal axis during fetal development.
Although dynorphin has long been considered an endogenous opioid peptide with high affinity for the kappa-opioid receptor, its biological function remains uncertain. The high concentration of dynorphin peptides and kappa-opioid receptors in the hypothalamus suggest a possible role for dynorphin in neuroendocrine regulation. This review will summarize evidence that support a role for dynorphin in regulation of the developing hypothalamo-pituitary-adrenal (HPA) axis. Dynorphin can exert dual actions on adrenocorticotropin (ACTH) release: (i) via activation of hypothalamic kappa-opioid receptors leading to release of corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP), and (ii) via a non-opioid mechanism that involves N-methyl-D-aspartate (NMDA) receptors and prostaglandins, and which is not dependent on CRH or AVP. The primary site of action of dynorphin and NMDA appears to be the fetal hypothalamus or a supra-hypothalamic site. The non-opioid mechanism does not mature until a few days prior to parturition and is active for only the brief perinatal period. In contrast, the opioid mechanism behaves as a constitutive system with sustained activity from prenatal to postnatal life. It is likely that the two mechanisms may respond to different stress stimuli and play a different role during development.
Szeto
Hazel H
HH
Department of Pharmacology, LC-405, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA. hhszeto@med.cornell.edu
D000818:Animals; D004399:Dynorphins / Q000494:pharmacology* / Q000502:physiology*; D005314:Embryonic and Fetal Development / Q000502:physiology*; D005260:Female; D007030:Hypothalamo-Hypophyseal System / Q000196:embryology* / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology*; D010913:Pituitary-Adrenal System / Q000196:embryology* / Q000502:physiology; D011247:Pregnancy; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology
D010446:Peptide Fragments; D016194:Receptors, N-Methyl-D-Aspartate; C026843:dynorphin (1-13); D004399:Dynorphins