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Abstract

Inhibin binding protein in rats: Alternative transcripts and regulation in the pituitary across the estrous cycle 
Bernard,Daniel J.; Woodruff,Teresa K.
Molecular Endocrinology 15(4): 654-667
Publication date: 2001


Inhibin binding protein (InhBP) and the transforming growthfactor-ß (TGFß) type III receptor, betaglycan, havebeen identified as putative inhibin coreceptors. Here we cloned theInhBP cDNA in rats and predict that it encodes a large membrane-spanningprotein that is part of the Ig superfamily, as has been describedfor humans. Two abundant InhBP transcripts (4.4 and 1.8 kb)were detected in the adult rat pituitary. The larger transcript encodesthe full-length protein while the 1.8-kb transcript (InhBP-shortor InhBP-S) corresponds to a splice variant of the receptor.This truncated isoform contains only the N-terminal signal peptideand first two (of 12) Ig-like domains observed in the full-lengthInhBP (InhBP-long or InhBP-L). InhBP-S does not contain a transmembranedomain and is predicted to be a soluble protein. Betaglycanwas also detected in the pituitary; however, it was most abundantwithin the intermediate lobe. Although we also observed betaglycanimmunopositive cells in the anterior pituitary, they rarely colocalizedwith FSHß-producing cells. We next examined physiological regulationof the coreceptors across the rat estrous cycle. Like circulatinginhibin A and inhibin B levels, pituitary InhBP-L and InhBP-SmRNA levels were dynamically regulated across the cycle and werenegatively correlated with serum FSH levels. Expression of both formsof InhBP was also positively correlated with serum inhibin B,but not inhibin A, levels. These data are particularly interestingin light of our in vitro observations that InhBP may functionas an inhibin B-specific coreceptor. Pituitary betaglycan mRNAlevels did not fluctuate across the cycle nor did they correlatewith serum FSH. These observations, coupled with its patternof expression within the pituitary, indicate that betaglycanlikely functions as more than merely an inhibin coreceptor withinthe pituitary. A direct role for InhBP or betaglycan in regulationof pituitary FSH by inhibin in vivo has yet to be determined,but the demonstration of dynamic regulation of pituitary InhBPand its negative relation to serum FSH across the estrous cycleis an important step in this direction.