Steroidogenic factor-1 (SF-1) and the regulation of expression of luteinising hormone and follicle stimulating hormone b-subunits in the sheep anterior pituitary in vivo.

ABSTRACT

Luteinising hormone (LH) and follicle stimulating hormone (FSH) comprise a common alpha-subunit and hormone-specific beta-subunit, are expressed in gonadotroph cells of the anterior pituitary and during the sheep oestrous cycle, are regulated by gonadotrophin releasing hormone (GnRH), ovarian peptides and steroids. Transcription factor steroidogenic factor-1 (SF-1) transactivates the common alpha-subunit and LH beta subunit in other species. We investigated whether SF-1 regulates beta-subunit expression and the regulation of SF-1 expression in vivo in sheep. Immunocytochemistry co-localised SF-1, LH and FSH to sheep pituitary gonadotrophs and electrophoretic mobility shift assays (EMSA) demonstrated that SF-1 bound to the LH beta promoter in vitro. No SF-1 DNA binding site was found in the FSH beta promoter. No difference in mean levels of SF-1, FSH beta, LH beta and GnRHr mRNA was measured between the luteal and follicular phases of the oestrous cycle. However SF-1 mRNA levels were correlated to those of LH beta in individual luteal phase animals (r = 0.88, p < 0.05), when the transcription rate of LH beta was significantly higher (p < 0.01). GnRH antagonist treatment of luteal animals did not produce a significant reduction in mRNA levels of LH beta, SF-1 and FSH beta. Administering oestradiol benzoate with GnRH antagonist reduced levels of SF-1 and FSH beta mRNA from luteal values (p < 0.005). We conclude that (1) expression of SF-1 is not solely dependent on GnRH and is downregulated by oestradiol; (2) the LH beta transcription rate is increased during the luteal phase but is not related to levels of LH beta or SF-1 mRNA; and (3) SF-1 does not appear to directly regulate expression of FSH beta, but may regulate expression indirectly.