Pituitary-related weight changes affecting the liver, uterus and adrenal glands of rats treated with hexoestrol and clomiphene in high doses.

The synthetic oestrogen hexoestrol, administered at 60 mg/kg/day for 4 days to female rats in 3 studies, caused the following mean changes in the relative weights of some of the principal organs: liver (+37%), spleen (-11%), adrenals (+43%), kidneys (+3%), pituitary (+23%), uterus (+49%), and ovaries (+13%). The heart weights showed no consistent changes. The mean relative organ weights of hypophysectomized, hexoestrol-treated rats did not differ significantly from those of untreated hypophysectomized controls. The latter animals had lower organ weights than sham-operated controls. Pretreatment with clomiphene citrate at dose levels of 20-60 mg/kg/day prevented in a dose-dependent manner most of the organ weight changes induced by hexoestrol. The exception was the adrenal weight, which was increased. Compared with controls, the mean relative organ weights of rats receiving clomiphene alone at 60 mg/kg/day differed as follows: liver (-18%), spleen (-17%), heart (-16%), adrenals (+7%), kidneys (-11%), pituitary (-13%), uterus (-25%), and ovaries (-4%). The changes affecting the liver, spleen, heart, kidneys and uterus were significant. Rats immunised with a monkey antiserum to rat growth hormone and treated with hexoestrol had significantly lower relative liver weights than did animals treated with hexoestrol alone. No other significant differences were observed. It is tentatively concluded that there is a mediating or co-operative pituitary influence involved in the significant hepatic, uterine and adrenal weight gains caused by hexoestrol. Clomiphene may act centrally to affect these organ weight changes and, indeed, may act at this level to (mainly) anti-organotrophic effect even in the absence of exogenous oestrogen. In the case of the hexoestrol-induced liver enlargement, the role of pituitary growth hormone is worth further investigation.