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

The β-subunits of luteinizing hormone (LHβ) and follicle-stimulating hormone (FSHβ) 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 FSHβ could be altered to that of LHβ, a truncated ovine FSHβ (oFSHβ) gene, which would encode a mRNA lacking the putative destabilizing 3′ untranslated region, was fused downstream of the ovine LHβ (oLHβ) promoter and expressed in transgenic mice. In two independent lines, line 16 and 17, we measured oFSHβ, mouse LHβ (mLHβ) and mouse FSHβ (mFSHβ) mRNA levels: (i) after castration in males; (ii) after administering inhibin to ovariectomized mice; and (iii) during the oestrous cycle. In each experiment, the expression profile of oFSHβ mRNA mimicked mLHβ and not mFSHβ mRNA. In addition, after actinomycin D treatment of pituitary cultures, while mFSHβ mRNA did decay, there was no measurable decay of the oFSHβ mRNA transcript. These differences increased total FSHβ steady-state mRNA expression levels in male transgenics. However, there was no detectable increase in pituitary FSH by either radioimmunoassay or western blotting analysis of pituitary extracts. Subsequent analysis revealed that pituitary FSHβ in line 16 was heavily glycosylated; in contrast, pituitary FSHβ in line 17 was largely unmodified. These differences in post-translational modification of the β-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 oFSHβ mRNA was manipulated to mimic mLHβ mRNA and this increased FSHβ mRNA expression levels, but did not increase storage of FSH. This suggests that, regardless of the levels of synthesis, post-translational sorting preferentially promotes FSH secretion from the pituitary.