The nuclear receptor steroidogenic factor 1 acts at multiple levels of the reproductive axis.
Steroidogenic factor 1 (SF-1), an orphan nuclear receptor, regulates the enzymes that produce sex steroids, and disruption of the Ftz-F1 gene encoding SF-1 precludes adrenal and gonadal development. We now study the role of SF-1 at other levels of the hypothalamic/pituitary/gonadal axis. In Ftz-F1-disrupted mice, immunohistochemical analyses with antibodies against pituitary trophic hormones showed a selective loss of gonadotrope-specific markers, supporting the role of SF-1 in gonadotrope function. In situ hybridization analyses confirmed these results; pituitaries from Ftz-F1-disrupted mice lacked transcripts for three gonadotrope-specific markers (LH beta, FSH beta, and the receptor for gonadotropin-releasing hormone), whereas they exhibited decreased but detectable expression of the alpha-subunit of glycoprotein hormones. SF-1 transcripts in the developing mouse pituitary, which first became detectable at embryonic day 13.5-14.5, preceded the appearance of FSH beta and LH beta transcripts. In adult rat pituitary cells, SF-1 transcripts colocalized with immunoreactivity for the gonadotrope-specific LH. Finally, SF-1 interacted with a previously defined promoter element in the glycoprotein hormone alpha-subunit gene, providing a possible mechanism for the impaired gonadotropin expression in Ftz-F1-disrupted mice. These studies establish novel roles of this orphan nuclear receptor in reproductive function.
Ingraham
H A
HA
Department of Physiology, University of California at San Francisco 94143-0556.
Lala
D S
DS
Ikeda
Y
Y
Luo
X
X
Shen
W H
WH
Nachtigal
M W
MW
Abbud
R
R
Nilson
J H
JH
Parker
K L
KL
D000818:Animals; D001483:Base Sequence; D015415:Biomarkers; D004247:DNA / Q000235:genetics; D015342:DNA Probes / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000235:genetics; D051717:Fushi Tarazu Transcription Factors; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins; D007986:Luteinizing Hormone / Q000235:genetics; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D010902:Pituitary Gland / Q000254:growth & development / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000502:physiology*; D012098:Reproduction / Q000235:genetics / Q000502:physiology*; D054339:Steroidogenic Factor 1; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
D015415:Biomarkers; D015342:DNA Probes; D004268:DNA-Binding Proteins; D051717:Fushi Tarazu Transcription Factors; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D054339:Steroidogenic Factor 1; D014157:Transcription Factors; C515058:steroidogenic factor 1, mouse; C515060:steroidogenic factor 1, rat; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D004247:DNA