Developmental defects of the ventromedial hypothalamic nucleus and pituitary gonadotroph in the Ftz‐F1 disrupted mice

• Published in: Developmental dynamics 1995-09, Vol.204 (1), p.22-29
• Main Authors: Shinoda, Koh, Lei, Hong, Yoshii, Hironori, Nomura, Masatoshi, Nagano, Mamoru, Shiba, Hiroharu, Sasaki, Hiroshi, Osawa, Yoshio, Ninomiya, Yasuharu, Niwa, Ohtsura, Morohashi, Ken‐Ichirou, Li, En
• Format: Article
• Language: English
• Subjects: Animals; Brain - abnormalities; Brain - embryology; Brain - physiology; Brain aromatase; DNA-Binding Proteins - physiology; Dorsomedial hypothalamic nucleus; Drosophila melanogaster - genetics; Drosophila Proteins; FTZ‐F1/Ad4BP; Fushi Tarazu Transcription Factors; Gene Expression Regulation, Developmental - physiology; Gene targeting; Gonadotroph; Homeodomain Proteins; Immunohistochemistry; Insect Proteins; Mice; Mice, Transgenic - embryology; Morphogenesis; Pituitary Gland - abnormalities; Pituitary Gland - embryology; Pituitary Gland - physiology; Rats; Receptors, Cytoplasmic and Nuclear; Receptors, Steroid - genetics; Steroidogenic Factor 1; Steroidogenic P450; Transcription Factors - genetics; Transcription Factors - physiology; Ventromedial hypothalamic nucleus; Ventromedial Hypothalamic Nucleus - embryology; Zinc Fingers - physiology
• ISSN: 1058-8388; 1097-0177
• DOI: 10.1002/aja.1002040104

Ad4BP (or SF‐1) has been identified as a transcription factor which regulates all the steroidogenic P450 genes in the peripheral organs, and is encoded by the mammalian homologue of Drosophila FTZ‐F1 gene. mRNA coding for Ad4BP was detected in the hypothalamus and pituitary of rats by RT‐PCR. Immunohistochemical analyses using an antiserum to Ad4BP in the brain and pituitary revealed that the transcription factor is expressed in nuclei of the dorso‐medial part of the ventromedial hypothalamus (dmVMH) and in some subpopulation of the adenohypophysial cells. Double immunostaining of the pituitary for Ad4BP and trophic peptide hormones, FSH, TSH, and ACTH, indicated a restricted localization of Ad4BP to the gonadotroph. Disruption of the mouse Ftz‐F1 gene was clarified to induce severe defects in the organization of the dmVMH and the function of the pituitary gonadotroph. However, some of the dm VMH neurons and pituitary gonadotrophs persisted, which provided a sharp contrast to complete agenesis of the peripheral steroidogenic tissues (adrenal and gonads) in the mutant mouse. Additional abnormalities were seen in the ventrolateral part of VMH and dorsomedial hypothalamic nucleus, both of which do not express Ad4BP but have strong reciprocal fiber‐connections with the dmVMH. Aromatase P450‐containing cells in the medial preoptico‐amygdaloid region, which were devoid of Ad4BP, persisted even in the brain of the gene disrupted mice. The present results clearly showed that the hypothalamic and pituitary Ad4BPs are essential to normal development of the functional VMH and gonadotroph through some mechanism distinct from that in the peripheral steroidogenic tissues. © 1995 wiley‐Liss, Inc.