The RET/GFRa/GDNF system displays a wide distribution in tissues such as nervous system, kidneys, intestine or testis. RET has been implicated in human pathologies. RET is a tyrosine-kinase receptor activated by four ligands GDNF, NTN, ART and PSPN through four co-receptors GFRa1, 2, 3 and 4 respectively. Activation of the receptor leads to cell differentiation or proliferation. Our group has shown that RET is expressed specifically in the somatotrope (GH) adult cell population within the pituitary, both in rats and in humans (Urbano, Endocrinology2000; Japon, JCEM2002) and provided evidence that RET expression controls the number of somatotropes in vivo inducing apoptosis (vs survival) through overexpression of Pit-1 (Cañibano, EMBOJ2007).
Here we characterize the mRNA levels of RET receptor by q-RT-PCR during the maturation of the pituitary from birth to adulthood.
Adenopituitaries of 24 hour, 10, 20, 30, 60 (adults) and 90 days-old rats were isolated and frozen.
Specific primers were used for: GRFa2, a positive control of inmature gland since is expressed in embryonic pituitary (Golden, ExpNeurol1999); Pit-1, essential for development of somatotropes, lactotropes and thyrotropes; GH, a control of pituitary growth maturation.
Expression of GFRa2 was high in newborn pituitaries and decreased with age. Opposite, GH levels were low during the first 10 days and they doubled its expression at 20 days around puberty remaining high through adulthood. It was observed that Pit-1 and Ret showed similar patterns of expression: both were expressed at birth at low quantities; at 10 days a peak of RET expression was seen decaying at 20 days; Pit-1 also increased its expression at 10 days but peaked at 20 days to decay later.
In summary, during growth expression of RET precedes a Pit-1 surge of expression just before the GH raise characteristic of puberty. This suggests that RET controls somatotrope cell generation in the pituitary.
03 - 07 May 2008
European Society of Endocrinology