Endocrine Abstracts (2002) 4 P70

Pituitary gonadotrophs in neuronal nitric oxide synthase (nNOS) knockout mice

E Fryer & JF Morris

Department of Human Anatomy and Genetics, University of Oxford, Oxford, UK.

Nitric oxide (NO) is a regulator of pituitary gonadotrophs via local paracrine and autocrine actions. Gonadotrophs express neuronal nitric oxide synthase (nNOS) but the effects of NO on gonadotrophs are controversial and both stimulation and inhibition of LH release has been reported. nNOS -/- mice have reduced fertility, but this is attributed to ovary actions, because no difference was detected in basal or GnRH-stimulated LH release (Klein et al 1998). We have therefore examined the gonadotroph cells of nNOS -/- and +/+ mice, comparing the number and size of cells, and their secretory vesicle population. Male and female wild-type (WT) and nNOS -/- mice (n = 4, 4, 4, 4) were examined. Both WT and -/- females had estrous cycles which were irregular, but animals were selected when the vaginal smear clearly indicated proestrus in a 4- or 5-day cycle. The animals were terminally anaesthetised and the tissues prepared for confocal microscopy to detect the number of LH-immunoreactive gonadotrophs, and for electron microscopy to analyse the secretory status of the cells. Knockout of nNOS had no apparent effect on the number of gonadotrophs. In females but not males the gonadotrophs were significantly smaller and contained less rough endoplasmic reticulum (ER) than those in WT mice. The secretory vesicles were smaller in female than in male mice of both genotypes but, in both sexes, the vesicles were larger in the knockout than the WT animals. These data suggest that, in both sexes there is a reduction in secretory vesicle turnover (indicated by the larger vesicles) and in the females significantly less active gonadotrophs (smaller, less rough ER). Such changes are consistent either with a reduction in NO-stimulated GnRH release from the hypothalamus or with a diminished intrapituitary stimulatory effect of NO. The role of gonadotroph derived NO remains to be determined.

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