Normal Reproductive Function in InhBP/p120-Deficient Mice

Abstract

The inhibins are gonadal transforming growth factor β superfamily protein hormones that suppress pituitary follicle-stimulating hormone (FSH) synthesis. Recently, betaglycan and inhibin binding protein (InhBP/p120, also known as the product of immunoglobulin superfamily gene 1 [IGSF1]) were identified as candidate inhibin coreceptors, shedding light on the molecular basis of how inhibins may affect target cells. Activins, which are structurally related to the inhibins, act within the pituitary to stimulate FSH production. Betaglycan increases the affinity of inhibins for the activin type IIA (ACVR2) receptor, thereby blocking activin binding and signaling through this receptor. InhBP/p120 may not directly bind inhibins but may interact with the activin type IB receptor, ALK4, and participate in inhibin B's antagonism of activin signaling. To better understand the in vivo functions of InhBP/p120, we characterized the InhBP/p120 mRNAs and gene in mice and generated InhBP/p120 mutant mice by gene targeting in embryonic stem cells. InhBP/p120 mutant male and female mice were viable and fertile. Moreover, they showed no alterations in FSH synthesis or secretion or in ovarian or testicular function. These data contribute to a growing body of evidence indicating that InhBP/p120 does not play an essential role in inhibin biology.

ACKNOWLEDGMENTS

Daniel J. Bernard and Kathleen H. Burns contributed equally to this work and share first authorship on this paper.

We acknowledge the assistance of the Ligand Core Facility, supported by NICHD/NIH through agreement U54 HD28934 as part of the Specialized Cooperative Centers Program in Reproduction Research, and T. Rajendra Kumar for his help in the evaluation of tissues from the knockout mice. Dan Philips also provided valuable technical assistance. Sally Camper (University of Michigan) and Dan Linzer (Northwestern University) supplied mouse POMC, prolactin, and growth hormone constructs.

The research was supported by grants CA60651 (M.M.M.) and HD037096 (T.K.W.) from the National Institutes of Health, which also provided research recovery funds after tropical storm Allison, and by a Lalor Foundation postdoctoral fellowship (D.J.B.). K.H.B. is a student in the Medical Scientist Training Program, supported in part by NIH grant T32GM-07330.