Molecular genetics of Insulin3

Abstract

A critical aspect in mammalian development is the acquisition of a sexually dimorphic phenotype. The genetic sex, determined at fertilization by the inheritance of either a X or Y chromosome, directs the bipotential gonad to differentiate into either testes or ovaries. In males, expression of the Y-specific gene Sry in the genital ridge initiates a chain of events that induces differentiation of the uncommitted gonad into testes. Testes in turn express molecules that specify secondary traits of male sexual differentiation. At least three hormones have been shown to be important for male differentiation: a) Mullerian inhibiting substance (MIS), produced by Sertoli cells, specifics the regression of the Mullerian ducts which give rise to the uterus in the female; b) androgens, produced by Leydig cells, direct the differentiation of multiple male accessory organs including: the vas deferens, seminal vesicle, prostate, the second phase of testicular descent, and external male genitalia and finally c) Insulin 3 (INSL3), a hormone of the Insulin family involved in mediating the first phase of testicular descent, another specific aspect of male sexual differentiation. In this chapter, experiments addressing the role of INSL3 in male sexual differentiation and in particular its function in testicular descent are described and discussed.