Expression of follicle stimulating hormone-receptor mRNA during gonadal development

Abstract

Receptors for follicle-stimulating hormone (FSH) are found only in the gonads and have been localised to the Sertoli cells of the testis and the granulosa cells of the ovary. During gonadal development, functional signal transduction systems are present before gonadotrophin receptors appear indicating the expression of the receptors is the crucial step in development of gonadal responsiveness to gonadotrophins. The FSH receptor gene contains a single large exon which encodes the transmembrane and intracellular domains and nine smaller exons which encode most of the extracellular domain. In all species studied so far the FSH-receptor primary transcript has been shown to undergo alternate splicing. The function of these alternate transcripts is unclear but changes in alternate splicing appear to be associated with development of receptor mRNA expression. In the rat transcripts encoding only the extracellular domain of the receptor are detectable 2 days before transcripts encoding the full length receptor. In the mouse ovary FSH-receptor mRNA levels and alternate splicing has been measured during development. Results show that FSH-receptor mRNA is detectable in day 1 ovaries which contain only primordial follicles. At this stage mRNA levels are low but a significant increase in FSH-receptor mRNA is seen around day 5 when primary follicles first appear. This correlates with in situ hybridisation studies which first detect FSH-receptor transcripts in primary follicles. At all stages of development the level of transcripts encoding the extracellular domain was significantly greater than that encoding for the transmembrane and intracellular regions suggesting that significant levels of shortened transcripts are produced. In the hypogonadal ( hpg) mouse which lacks circulating gonadotrophins levels of FSH-receptor mRNA appeared normal up to 15 days. This shows that gonadotrophins are not required for development of FSH-receptor mRNA levels. Studies on FSH-receptor mRNA levels during granulosa cell luteinization show that there is complete loss of full-length transcripts soon after luteinization. Transcripts encoding the extracellular domain remain present, however, up to at least mid-cycle. Thus, changes in receptor transcript splicing during loss of FSH-receptors appear to mimic, in reverse, changes occurring during development. It may be that the FSH-receptor gene is constitutively expressed in follicular (pre-granulosa) cells, granulosa cells and granulosa-luteal cells but that control of RNA splicing regulates levels of full-length FSH-receptor transcript.