Characterisation of the pituitary gonadotrophs of FSH‐receptor knockout mice

Abstract

To investigate further brain‐pituitary‐gonadal interrelationships we have generated mice in which the gene encoding the FSH receptor has been disrupted (FSHRKO). FSHRKO females but not males are infertile. Compared with control animals, serum concentrations of LH and FSH and pituitary content of FSH are significantly increased in female FSHRKO (Abel et al. Endocrinology141, 2000). The aim of the present study was to correlate these physiological differences in gonadotroph function of 8‐week‐old‐female normal and FSHRKO mice with a structural analysis of their gonadotrophs. Gonadotrophs were identified by LH‐immunogold labeling for electron microscopy and gonadotroph frequency estimated from 1 (m sections immunolabelled for LH. In FSHRKO the frequency, cell and nuclear profile areas of gonadotrophs did not differ significantly from that in normal mice. Surprisingly the endoplasmic reticulum appeared normal and undilated despite the lack of oestradiol feedback in the KO animals. LH‐immunoreactive cells in female FSHRKO had significantly (P < 0.05) larger secretory granules 176(7 nm) diameter, mean(SEM) compared to normal mice 139(7 nm) but there was no significant difference in the granule area/cytoplasmic area. The subpopulation of granules in which an electron‐dense core was present in a more electron‐lucent ‘halo’ was absent in FSHRKO gonadotrophs. The increased pituitary FSH stores in FSHRKO mice therefore appear to be represented by the formation of larger secretory granules in which the packaging of hormone is less dense. Interestingly, despite being infertile and lacking biologically active estrogen, the alterations in FSHRKO pituitary morphology are relatively subtle compared to normal mice.