Developmental defects of the ventromedial hypothalamic nucleus and pituitary gonadotroph in the Ftz-F1 disrupted mice.
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 dorsomedial 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.
Shinoda
K
K
Department of Anatomy II, Kinki University School of Medicine, Osakasayama.
Lei
H
H
Yoshii
H
H
Nomura
M
M
Nagano
M
M
Shiba
H
H
Sasaki
H
H
Osawa
Y
Y
Ninomiya
Y
Y
Niwa
O
O
D000818:Animals; D001921:Brain / Q000002:abnormalities / Q000196:embryology / Q000502:physiology; D004268:DNA-Binding Proteins / Q000502:physiology; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000235:genetics; D051717:Fushi Tarazu Transcription Factors; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D018398:Homeodomain Proteins; D007150:Immunohistochemistry; D019476:Insect Proteins; D051379:Mice; D008822:Mice, Transgenic / Q000196:embryology*; D009024:Morphogenesis; D010902:Pituitary Gland / Q000002:abnormalities / Q000196:embryology* / Q000502:physiology; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid / Q000235:genetics*; D054339:Steroidogenic Factor 1; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology; D014697:Ventromedial Hypothalamic Nucleus / Q000196:embryology*; D016335:Zinc Fingers / Q000502:physiology
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D051717:Fushi Tarazu Transcription Factors; D018398:Homeodomain Proteins; D019476:Insect Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D054339:Steroidogenic Factor 1; D014157:Transcription Factors; C497169:ftz protein, Drosophila; C499712:nuclear hormone receptor FTZ-F1, Drosophila