Comparative localization of Dax-1 and Ad4BP/SF-1 during development of thehypothalamic-pituitary-gonadal axis suggests their closely related and distinct functions

Two nuclear receptors, Ad4BP/ SF-1 and Dax-1, are essential regulators for development and function of the mammalian reproductive system. Similarity i n expression sites, such as adrenal glands, gonads, pituitary, and hypothal amus, suggests a functional interaction, and the phenotype similarities wer e manifested in Ad4BP/SF-1-deficient mice and in cases of natural human mut ations of Dax-1. In this study, quantitative reverse transcriptase polymera se chain reaction analyses revealed that expression profiles of Dax-1 in em bryonic gonads are different between the two sexes and also from those of A d4BP/SF-1. Immunohistochemical analyses clarified the spatial and temporal expressions of the Dax-1 protein during development of tissues composing th e hypothalamic-pituitary-gonadal axis. During gonadal development, Dax-1 oc curred after Ad4BP/SF-1 exhibiting a sexually dimorphic expression pattern at indifferent stages, indicating a possibility of Dax-1 involvement in ear liest sex differentiation. When cord formation begins in the testis at embr yonic day 12.5 (E12.5), Dax-1 was expressed strongly in Sertoli cells, but its expression level markedly decreased in Sertoli cells and increased in i nterstitial cells between E13.5 and E17.5. In the female, Dax-1 was strongl y expressed in the entire ovarian primordium from E12.5 until E14.5, and th en its expression level was decreased and limited to cells near the surface epithelium between E17.5 and postnatal day 0 (P0). During postnatal develo pment of the testis, the variable staining of Dax-1 in Sertoli cells was de tected as early as P7 and Dax-1-expressing Leydig cells became rare. In the postnatal ovary, Dax-1 expression was detected in granulosa cells with var iable staining intensity, and occasionally in interstitial cells. During pi tuitary organogenesis, Dax-1 but not Ad4BP/SF-1 was expressed in the dorsal part of Rathke's pouch from E9.5. Later in development after E14.5, the di stribution of Dax-1 overlapped with that of Ad4BP/SF-1, being restricted to gonadotropic cells in the anterior pituitary. In the ventromedial hypothal amus (VMH), Dax-1 and Ad4BP/SF-1 were mostly colocalized throughout the emb ryonic and postnatal development. Thus, the coexpression of Dax-1 and Ad4BP /SF-1 indicates their closely related functions in the development of the r eproductive system. Furthermore, we noticed the presence of cells that expr ess Dax-1 but not Ad4BP/SF-1, further indicating additional functions of Da x-1 in an Ad4BP/ SF-1independent molecular mechanism. (C) 2001 Wiley-Liss, Inc.