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Human Reproduction, Vol. 8, No. suppl_2, pp. 29-36, 1993
© 1993 European Society of Human Reproduction and Embryology

Regulation of gonadotrophin subunit gene expression

R.N. Clayton

Department of Medicine, School of Postgraduate Medicine, University of Keele Stoke-on-Trent, Staffordshire, UK

Physiological regulation of gonadotrophin subunit gene expression was investigated in vivo by cDNA–mRNA hybridization from individual pituitary glands from rats and mice. Common {alpha}, LH-β, FSH-β mRNA increased in a timedependent manner after orchidectomy and ovariectomy rats, the increases being prevented by testosterone and oestradiol, respectively, in male and female rats. Increases in all three subunit mRNAs after gonadectomy were prevented by a GnRH antagonist and antiserum, and were reduced by the same treatments in intact rats, indicating thendependence on endogenous GnRH. Further evidence for GnRH influences on gonadotrophin gene activation comes from pulsatile GnRH treatment of GnRH deficient hypogonadotrophic hypogonadal mice in which this induced {alpha} and LH-β mRNA to supranormal and normal values, respectively. Pituitary desensitization with GnRH agonist infusion markedly suppressed LH-β and FSH-β mRNA levels and pituitary LH accumulation, but paradoxically increased a subunit mRNA to castrate levels in intact rats and failed to suppress {alpha} mRNA in castrated rats. These results indicate the divergent regulation of {alpha} and specific LH-β/FSH-β mRNA in vivo and that the latter are closely related to LH/FSH synthesis and secretion and physiological GnRH stimulation the pituitary. In-vitro studies suggest that physiological GnRH induces transcription from β subunit genes and also stabilizes their mRNAs, possibly by altering mRNA length. Preliminary studies to investigate regulatory elements in the 5' region the LH-β gene suggest the presence of an atypical cAMP responsive element since an LH-β-CAT construct can be induced by 3-fold in a transient heterologous cell expression system.

Key words: FSH-β subunit/gene expression/gonadotrophin/LH-βsubunit/pituitary


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