New insights in the mechanism by which SRIF influences GH secretion.
Once thought to act only as a somatotropin release-inhibiting factor (SRIF), SRIF is currently viewed as a pleiotropic neuroendocrine factor controlling secretion, gene expression, apoptosis and signalling in many different targets. Actually, despite the numerous studies that have characterized SRIF action on somatotropes, new facets are continuously being discovered which help enlightening the biology of this cell type. As an example, ten years ago we demonstrated that SRIF exerts a dual, inhibitory/stimulatory effect on GH release from cultured pig somatotropes, which depends on the concentration of the peptide and on a divergent responsiveness of the two main cell subsets comprising the somatotrope population. Specifically, very low, picomolar doses of SRIF were found to stimulate GH release in vitro from intact cultures of dispersed pig pituitary cells and from purified somatotrope subpopulations. Conversely, higher (10(-7)M) SRIF concentrations inhibited, as expected, GHRH-induced GH release from intact pituitary cells and from one of the somatotrope subtypes; yet, at this same dose, it stimulated GH release from the other somatotrope subset. Analysis of second messenger pathways revealed that cAMP is the main signal conveying the stimulatory effects of low-dose SRIF. This peptide also exerts a distinct, dose-dependent regulation of the expression of three of its receptor subtypes (sst1, sst2 and sst5) at the pituitary. Indeed, acute in vitro treatment with a high SRIF dose increased mRNA levels of all three subtypes, whereas a low SRIF concentration only increased that of sst5. Interestingly, short term treatment with GHRH or ghrelin reduced the expression of sst5, and not that of sst1 and sst2. Hopefully, ongoing studies on cloning and individual characterization of porcine sst will help to unravel the complex and exciting response of somatotropes to SRIF.
Castaño
J P
JP
Department of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain. justo@uco.es
Delgado-Niebla
E
E
Durán-Prado
M
M
Luque
R M
RM
Sánchez-Hormigo
A
A
Gracia-Navarro
F
F
García-Navarro
S
S
Kineman
R D
RD
Malagón
M M
MM
D000818:Animals; D013006:Growth Hormone / Q000378:metabolism*; D006801:Humans; D009490:Neurosecretory Systems / Q000378:metabolism*; D013004:Somatostatin / Q000378:metabolism*
D013004:Somatostatin; D013006:Growth Hormone