Isoforms and half-life of FSH from sheep with different reproductive states

Abstract

The glycoprotein hormone FSH comes in many different isoforms. In humans and rats the charges of the FSH isoforms vary with reproductive state and these affect the half-life of FSH in plasma. In this study we examined the charge heterogeneity of FSH in pituitary extracts from sheep with different reproductive states. Also the half-life of clearance of pituitary FSH from the different reproductive states was determined in mice. Pituitaries were collected from: anoestrous, luteal phase, follicular phase, early-pregnant and late-pregnant ewes, ewe lambs, ram lambs, rams during the breeding and non-breeding seasons and wethers (5 per group). After extraction, FSH isoforms were fractionated by HPLC anion exchange chromatography. The volume at which half of the FSH had eluted from the ion exchange column was determined (HP(50)). It was found that FSH isoforms from ewes (HP(50)=96.7+/- 1.3 ml (s.e.m. )) eluted later (P<0.01) than those from rams (HP(50)=82.3+/-1.3 ml) indicating that FSH isoforms in the ewes were more acidic than those from rams. There was a seasonal difference in ewes, with ewes in anoestrus (HP(50)=101.6+/-2.6 ml) having more-acidic (P<0.01) FSH isoforms than the ewes during the oestrous cycle (HP(50)=95.3+/-0.7 ml). There was an effect of age, with the FSH isoforms from cycling ewes (HP(50)=95.3+/- 0.7 ml) being more acidic (P<0.01) than those from ewe lambs (HP(50)=88.3+/-1.9 ml). There was an effect of pregnancy, with late-pregnant ewes (HP(50)=107.3+/- 1.6 ml) having more-acidic FSH isoforms (P<0.05) than those from anoestrous ewes (HP(50)=101.6+/-2.6 ml) and there was an effect of castration with the breeding season rams (HP(50)=80.7+/-1.4 ml) having more-acidic (P<0.05) FSH isoforms than wethers (HP(50)=74.0+/-0.5 ml). The half-life of pituitary FSH from animals in the different reproductive states was found to be negatively correlated with HP(50) (r(2)=0.56, P<0.01). The FSH isoforms from wethers were the least acidic and had the longest half-lives. Collectively, these findings show that in sheep, age, sex and reproductive state are all factors which influence the forms of FSH that are extracted from the pituitary gland. Moreover, these results demonstrate that FSH from sheep with the most-acidic FSH isoforms have the shortest half-life in plasma.