Evidence that corticotropin-releasing hormone acts as a growth hormone-releasing factor in a primitive teleost, the European eel (Anguilla anguilla)

The inhibitory control of growth hormone (GH) release by somatostatin (SRIH ) has been conserved throughout vertebrate evolution, In contrast, the neur opeptides involved in the stimulatory control of GH vary according to speci es and/or physiological situations. We investigated the direct pituitary re gulation of GH release in a primitive teleost, the European eel (Anguilla a nguilla L.) at the juvenile stage. Short-term serum-free primary cultures o f dispersed pituitary cells were used, and GH release was measured by an ho mologous radioimmunoassay. Whereas growth hormone-releasing hormone (GHRH), gonadotropin-releasing hormone (GnRH), thyrotropin-releasing hormone (TRH) , neuropeptide Y (NPY) and cholecystokinin (CCK) failed to induce any chang e in GH release, corticotropin-releasing hormone (CRH) dose-dependently sti mulated GH release with a significant effect at 1 nM and a maximal effect ( greater than or equal to 400% of controls at 24 h) at 100 nM. In agreement with our previous studies, PACAP also stimulated GH release but its maximal effect was lower than that of CRH. Proopiomelanocortin (POMC)-peptides, co rticotropin (ACTH), melanotropin (alpha-MSH), beta-endorphin) had no effect on GH release, at any dose tested (0.1-1000 nM), indicating that the stimu latory effect of CRH on GH release by somatotrophs was not mediated by CRH- induced release of POMC-peptides from corticotrophs and melanotrophs. The C RH antagonist, alpha-helical CRH(9-41), significantly inhibited the stimula tory effect of CRH on GH release, suggesting the implication of specific CR H receptors related to mammalian ones. The stimulatory effect of CRH on GH release was reduced after 24 h of incubation, indicating a desensitization. In contrast, no desensitization to the inhibitory effect of SRIH was obser ved. SRIH inhibited CRH action in a dose-dependent manner. The effect of SR IH was overriding, 1 nM SRIH being able to abolish the effect of 1000 nM CR H. In conclusion, in the eel, CRH stimulates GH release directly at the pit uitary cell level. GH and cortisol secretions could interact in controlling several physiological functions such as metabolism and ion exchange. This study suggests that CRH may have played an important early role in vertebra tes co-ordinating the activation of various endocrine axes involved in meta morphosis, osmoregulation, stress and fasting. The stimulatory role of CRH on GH release may have been partially conserved during evolution, as it is found in some human physic-pathological situations such as stress, fasting and depression.