Endocrine Abstracts (2006) 11 OC33

Efect of overexpression of GH secretagogue receptor (GHSR) in the pituitary of transgenic mice

LM Seoane1, D Carmignac2, FF Casanueva1 & ICAF Robinson2

1Molecular Endocrinology. Facultad de Medicina. Complejo hospitalario universitario de Santiago, Santiago de Compostela, Spain; 2National Institute for Medical Research, London, United Kingdom.

The expression of GHSR, an endogenous Ghrelin receptor, has been reported in pituitary, but the levels of expression of this receptor are low and the role of the GHSR in the normal physiology to directly affect GH or Prolactin release in pituitary remains unclear. We used a line of GH-GHSR transgenic mice to analyse the effects of hGHSR over-expression in the pituitary GH cells. We also crossed these mice with GH-GFP transgenic mice with fluorescent somatotrophs.

Objectives: (1) Breeding between GH-hGHS-R and GH-eGFP mice, to obtain double transgenic GH-GFPx hGHS-R mice. We obtained four differents groups: wild type, transgenic hGH-hGHS-R, transgenic mice GH -eGFP and double transgenic GH-eGFPxhGHS-R mice. (2) Colocalization studies. (3) Physiological studies.

Methods: PCR: genotyping. Radio Inmuno assay for GH and prolactin pituitary contents in the transgenic mice. Immunocytochemistry: to study the colocalization between GH, GHSR and prolactin.

Results: Overexpression of GHSR expression in the pituitary did not affected body weight but the GH pituitary content in transgenic mice was lower than in wild type mice. By inmunohistochemistry we found than only a few somatotroph cells detectably coexpressed GH and GHSR, and this was similar in males and females. Despite alterations in GH, pituitary prolactin content was not affected by the transgenes. In wild-type mice we could show: Colocalization between GHSR and prolactin, both in pituitary sections and in isolated pituitary cells. This suggests that the GHSR may have a role in regulating lactotroph function directly, consistent with earlier findings in dwarf rats.

Conclusions: Transgenic mice overexpressing GHSR maintain lower GH pituitary content, but this does not affect body weight or prolactin pituitary content. Pituitary cells expressing GHSR are expressing GH and/or prolactin, and the latter may suggest that GHS could affect prolactin physiology.

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