Evidence That Corticotropin‐Releasing Hormone Acts as a Growth Hormone‐Releasing Factor in a Primitive Teleost, the European Eel (Anguilla anguilla)

Abstract

The inhibitory control of growth hormone (GH) release by somatostatin (SRIH) has been conserved throughout vertebrate evolution. In contrast, the neuropeptides involved in the stimulatory control of GH vary according to species and/or physiological situations. We investigated the direct pituitary regulation of GH release in a primitive teleost, the European eel (Anguilla anguilla L.) at the juvenile stage. Short-term serum-free primary cultures of dispersed pituitary cells were used, and GH release was measured by an homologous 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 change in GH release, corticotropin-releasing hormone (CRH) dose-dependently stimulated GH release with a significant effect at 1 nM and a maximal effect (> or =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, corticotropin (ACTH), melanotropin (alpha-MSH), beta-endorphin) had no effect on GH release, at any dose tested (0.1-1000 nM), indicating that the stimulatory effect of CRH on GH release by somatotrophs was not mediated by CRH-induced release of POMC-peptides from corticotrophs and melanotrophs. The CRH antagonist, alpha-helical CRH(9-41), significantly inhibited the stimulatory effect of CRH on GH release, suggesting the implication of specific CRH 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 observed. SRIH inhibited CRH action in a dose-dependent manner. The effect of SRIH was overriding, 1 nM SRIH being able to abolish the effect of 1000 nM CRH. In conclusion, in the eel, CRH stimulates GH release directly at the pituitary 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 vertebrates co-ordinating the activation of various endocrine axes involved in metamorphosis, 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 physio-pathological situations such as stress, fasting and depression.

Evidence for a negative feedback in the control of eel growth hormone by thyroid hormones

“…2). The total amount of GH released into the medium over 12 days (18 1 µg/62 500 cells) represented 170% of the initial cell content (day 0: 11 1 µg/62 500 cells), reflecting active synthesis of GH during the culture, as reported previously (Rousseau et al , 1999. Addition of T 3 or T 4 (100 nM) significantly decreased GH release; the inhibitory effects of T 3 and T 4 were significant after 48 h of incubation (P<0·05) and were maintained up to the end of the culture on day 12 (P<0·001; Fig.…”

“…At the pituitary level, thyrotropinreleasing hormone (TRH) was shown to be able to stimulate not only thyrotropin (TSH) but also GH release in various vertebrates including mammals, birds, reptiles, amphibians (Harvey 1990a) and teleosts (Peng & Peter 1997). Moreover, corticotropin-releasing hormone (CRH) has been shown not only to stimulate corticotropin release but also to act as a GH-releasing factor and TSH-releasing factor in reptiles (Denver & Licht 1989) and in teleosts (Larsen et al 1998, Rousseau et al 1999.…”

Effects of cortisol and thyroid hormone on peripheral outer ring deiodination and osmoregulatory parameters in the Senegalese sole (Solea senegalensis)

“…However, we cannot exclude a feedback mechanism in which cortisol reduces the activity of hypothalamic corticotropin-releasing hormone (CRH), urotensin-I (UI), and thyrotropin-releasing hormone (TRH), factors with both corticotropic and thyrotropic activities in a number of fish species (reviewed by Bernier et al (2009)). Indeed, in salmonids and eels, CRH has thyrotropic activity in vitro (Larsen et al 1998, Rousseau et al 1999, and, in carp, the interaction between thyroid hormones and the HPI axis is illustrated by the up-regulation of hypothalamic crh-binding protein gene expression after T 4 treatment (Geven et al 2006). It could well be that hypothalamic factors of the HPI axis, namely CRH, UI, TRH, are altered after cortisol treatment in S. senegalensis and then, jointly with the hepatic and renal ORD pathway, have affected plasma fT 4 concentrations.…”

Molecular evolution of the growth hormone-releasing hormone/pituitary adenylate cyclase-activating polypeptide gene family. Functional implication in the regulation of growth hormone secretion

“…It should be noticed, however, that in the goldfish both type I PACAP receptor and a GHRH receptor are expressed in the pituitary (Chan et al 1998, Wong et al 1998), indicating that not only PACAP but also GHRH may exert some kind of hypophysiotropic activity. In addition, it has previously been shown that, in birds, amphibians and fish, several regulatory neuropeptides such as gonadotropin-releasing hormone (Marchant et al 1989, Lin et al 1993, Melamed et al 1995, neuropeptide Y (Peng et al 1990), thyrotropinreleasing hormone (Harvey et al 1978, GraciaNavarro et al 1991, Trudeau et al 1992, cholecystokinin (Himick et al 1993), bombesin (Himick & Peter 1995 and corticotropin-releasing hormone (Rousseau et al 1999) are involved in the control of somatotrope cell activity.…”