Endocrine Abstracts

Knockout studies have demonstrated that FSHbeta knockout (FSHbKO) and FSH receptor knockout (FSHRKO) female mice are infertile due to block of follicle development at the pre-antral stage. The ovaries are reduced in size and uteri are atrophic. However, a proportion of FSHRKO and FSHbKO mice develop ovarian and uterine hypertrophy in middle age (Abel et al, 2001). In order to investigate further brain-pituitary-gonadal interrelationships the aim of the present study was to compare pituitary gonadotrophs of 12 month old female normal mice with FSHRKO and FSHbKO mice either with uterine hypertrophy (large uterus >110g; lu) or without (small uterus <15g; su). Gonadotrophs were identified by electron microscopy and LH immunogold labeling, for comparing the size of cells and their secretory vesicles, and gonadotroph number was estimated from 1um sections immunofluorescence-labelled for LH (n=4 animals). The number of gonadotrophs in FSHRKO and FHSbKO was not significantly different to that in normal mice. LH-immunoreactive cells in female su and lu FSHRKO and FSHbKO were found to have significantly (P<0.01) larger secretory vesicles compared to normal mice and in lu FSHbKO and FSHRKO the number of granules/cytoplasmic area was significantly increased (P<0.01). Larger vesicles suggest a reduction in vesicle turnover whereas the increase in vesicle number represents elevated LH and FSH pituitary content in lu but not su mutant mice. Mutant gonadotrophs were not significantly different in size to normal mice, endoplasmic reticulum appeared normal and undilated and no marginalisation of vesicles to the cell perimeter was detected. Despite being infertile and lacking biologically active estrogen the alterations in FSHRKO and FSHbKO gonadotroph morphology are relatively subtle compared to normal mice. However, lu FSHbKO and FSHRKO gonadotrophs appear less active than normal and su gonadotrophs consistent with enhanced negative feedback and/or reduced GnRH drive of gonadotroph function in the presence of uterine hypertrophy.