Effect of chronic FSH administration on ovarian follicular development, ovulation rate and corpora lutea formation in sheep
Authors: McNatty K. P. , Hudson N. L. , Heath D. A. , Shaw L. , Blay L. , Berry L. , Lun S. 
Published: December 2008

This study in ewes examined the effects on ovarian function of a pulsatile regimen of ovine FSH (NIADDK-oFSH-17) administered over a 24- to 28-day period beginning on day 1 of the oestrous cycle (day 0 = oestrus). The FSH (1·66 μg or 5·00 μg) was administered i.v. over a 1-min interval once every hour throughout the treatment period. In other ewes ovine LH (NIDDK-oLH-23) was administered (10 μg once every 2 h) for 24–28 days together with oFSH (1·66 μg/h).

Compared with untreated controls (n = 19 ewes), FSH alone at both doses (n = 19 ewes/dose) as well as the FSH +LH treatment (n=10) led to significant increases in the plasma concentrations of FSH (P <0·01), ovarian weight (P <0·05) and ovulation rate (P <0·01) but there was no change in the mean weight of individual corpora lutea (CL). Exogenous FSH at the high but not the low dose alone or with LH stimulated a significant overall increase in plasma inhibin concentrations (P <0·05). The geometric mean (and 95% confidence limits) ovulation rates in the high FSH (i.e. 5·00 μg/h), low FSH (i.e. 1·66 μg/h), low FSH+LH, and control treatment groups were 15·3 (9·3, 24·8), 3·7 (2·1, 6·0), 3·7 (2·5, 5·8) and 1·4 (1·2, 1·7) respectively. The FSH or FSH+LH treatments did not alter the total numbers of antral follicles (≥1 mm diameter). However, the high but not the low FSH or low FSH + LH treatment led to significant increases in the mean numbers of large follicles (i.e. >4·5 mm diameter; P<0·01) and a higher proportion of non-atretic antral follicles.

Highly significant linear relationships were found between the mean plasma concentrations of FSH or inhibin and the ovulation rate (FSH: r=0·74, P<0·0001; inhibin: r=0·93, P<0·0001). Highly significant linear relationships were also found between the plasma concentrations of FSH or inhibin and the number of large follicles (i.e. >4·5 mm diameter; FSH, r=0·78, P<0·0001; inhibin, r=0·80, P<0·0001) and between the plasma concentrations of inhibin and the number of granulosa cells in large follicles (r=0·78, P<0·0001). After the high FSH but not the low FSH treatment there were significant increases in both FSH- and LH-induced responsiveness in granulosa cells with respect to cyclic AMP synthesis in vitro. In the high FSH treatment group, granulosa cells from 1–2·5 mm diameter follicles were responsive to LH whereas, in the low FSH or FSH + LH treatment groups and the controls, granulosa cells were not responsive to LH until the follicles were >4·5 mm in diameter. FSH or FSH+ LH treatment did not lead to increases in aromatase activity in granulosa cells (i.e. when expressed on a per cell basis) or to increases in oestradiol in follicular fluid.

Collectively these results show that chronic increases in plasma FSH concentrations influence, in a dose–responsive manner, the size distribution of antral follicles, the proportion of non-atretic follicles, the number of follicles with peak aromatase activity and the ovulation rate, without altering the total number of antral follicles, the granulosa cell composition of individual follicles or the sizes of individual CL. Exogenous FSH treatment at high but not low doses enhanced the sensitivities of granulosa cells to both FSH and LH in vitro. Increases in plasma FSH also led to higher concentrations of plasma inhibin as a consequence of an increase in the number of large follicles and thus the number of granulosa cells.

Journal of Endocrinology (1993) 138, 315–325