Rodin, David Andrew; (1991) A study of the pre-translational regulation of follicle-stimulating hormone synthesis by gonadotrophin-releasing hormone and gonadal steroids. Doctoral thesis (M.D), UCL (University College London).

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Abstract

In adult male and female rats and mice, there was, generally, a good qualitative correlation between follicle-stimulating hormone (FSH) B mRNA levels and overall FSH synthesis (as reflected by pituitary and serum FSH), indicating the physiological significance of this pre-translational regulation. Oestradiol treatment from the time of operation attenuated the postovariectomy increase in FSH B mRNA in female rats and mice, while testosterone reduced FSH B mRNA levels in acutely orchidectomized males. There were no major differences between these species in the regulation of FSH B gene expression by gonadal steroids, but the results suggest a role for additional gonadal inhibitory factor(s) in this feedback regulation. In chronically castrated rats, oestradiol suppressed FSH B mRNA levels rapidly in females, but testosterone increased FSH B mRNA in males. This variability of response to testosterone may reflect interactions with other regulatory factors. Abolition of gonadotrophin-releasing hormone (GnRH) stimulation of the pituitary by GnRH antagonist or antiserum treatment, and gonadotroph desensitization using a GnRH agonist, prevented the increases in FSH B mRNA in orchidectomized rats and reduced FSH B mRNA levels in intact rats. Changes in overall FSH biosynthesis occurred in parallel. These observations suggest that FSH B gene expression is GnRH-dependent, that GnRH is the major releasing factor for FSH, and that modulation of GnRH secretion is the principal target for gonadal steroid negative feedback. For in vitro studies of gene regulation, two bovine FSH B genomic DNA clones were isolated and characterized. However, neither contained upstream sequences, the likely location of hormone response elements. Whilst there are differences in the gonadal regulation of FSH B and luteinizing hormone (LH) B genes, GnRH exerts parallel effects on LH B and FSH B mRNA levels, suggesting that it provides a common primary stimulus for the induction of both B-subunit genes in vivo.

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