Manipulating the in vivo mRNA expression profile of FSH beta to resemble that of LH beta does not promote a concomitant increase in intracellular storage of follicle-stimulating hormone

The beta -subunits of luteinizing hormone (LH beta) and follicle-stimulatin g hormone (FSH beta) are differentially expressed, and this may contribute to the unique expression and storage patterns of LH and FSH. Therefore, to determine if the in vivo expression profile of FSH beta could be altered to that of LH beta, a truncated ovine FSH beta (oFSH beta) gene, which would encode a mRNA lacking the putative destabilizing 3' untranslated region, wa s fused downstream of the ovine LH beta (oLH beta) promoter and expressed i n transgenic mice. In two independent lines, line 16 and 17, we measured oF SH beta, mouse LH beta (mLH beta) and mouse FSH beta (mFSH beta) mRNA level s: (i) after castration in males; (ii) after administering inhibin to ovari ectomized mice; and (iii) during the oestrous cycle. In each experiment, th e expression profile of oFSH beta mRNA mimicked mLH beta and not mFSH beta mRNA. In addition, after actinomycin D treatment of pituitary cultures, whi le mFSH beta mRNA did decay, there was no measurable decay of the oFSH beta mRNA transcript. These differences increased total FSH beta steady-state m RNA expression levels in male transgenics. However, there was no detectable increase in pituitary FSH by either radioimmunoassay or western blotting a nalysis of pituitary extracts. Subsequent analysis revealed that pituitary FSH beta in line 16 was heavily glycosylated; in contrast, pituitary FSH be ta in line 17 was largely unmodified. These differences in post-translation al modification of the beta -subunit, and the lack of intracellular storage , contributed to increased plasma FSH levels and ovulation rate in line 16, but not line 17. In conclusion, the expression profile of oFSH beta mRNA w as manipulated to mimic mLH beta mRNA and this increased FSH beta mRNA expr ession levels, but did not increase storage of FSH. This suggests that, reg ardless of the levels of synthesis, post-translational sorting preferential ly promotes FSH secretion from the pituitary.