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Developmental defects of the ventromedial hypothalamic nucleus and pituitary gonadotroph in the Ftz‐F1 disrupted mice
Author(s) -
Shinoda Koh,
Lei Hong,
Yoshii Hironori,
Nomura Masatoshi,
Nagano Mamoru,
Shiba Hiroharu,
Sasaki Hiroshi,
Osawa Yoshio,
Ninomiya Yasuharu,
Niwa Ohtsura,
Morohashi KenIchirou,
Li En
Publication year - 1995
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/aja.1002040104
Subject(s) - biology , medicine , endocrinology , steroidogenic factor 1 , hypothalamus , nucleus , pituitary gland , gene , transcription factor , hormone , microbiology and biotechnology , genetics , nuclear receptor
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.