Effects of immunoneutralization of substance P on hypothalamic neurotransmitters in normal mice and in transgenic mice expressing bovine growth hormone.

Abstract

It is well known that transgenic mice expressing bovine growth hormone have altered neuroendocrine functions. Substance P was shown to influence the secretion of gonadotropins. In this investigation, the effect of a single injection of an antiserum to substance P was investigated in intact and castrated transgenic (MT-bGH) mice and in their normal litter mates. In the median eminence, the administration of antisubstance P serum resulted in a decreased dihydroxyphenyl acetic acid/dopamine index in intact and castrated normal mice but was without effect in transgenics. The homovanillic/dopamine index was decreased in normal mice (intact or castrated) but unchanged in transgenics. Norepinephrine and epinephrine were increased in normal mice (intact and castrated) treated with the anti-SP serum, but in transgenic mice, the anti-SP serum induced significant changes of norepinephrine only in intact animals, with no modifications in epinephrine levels. In the whole hypothalamus (minus the median eminence), the injection of antisubstance P serum resulted in an increased dihydroxyphenyl acetic acid/dopamine index in castrated, but not in intact, normal mice. In transgenic mice, this index was increased in intact but decreased in castrated animals. The homovanillic/dopamine index was decreased in normal intact mice treated with the antiserum but increased in intact transgenic mice. Norepinephrine and epinephrine were decreased by the antiserum treatment in normal intact mice but were unchanged in transgenics, except for norepinephrine in castrated transgenics, in which it was found increased. The administration of the antiserum did not affect plasma LH, FSH, or prolactin in normal mice but it reduced LH levels in intact transgenic mice. These results indicate that the response to the treatment with the antiserum to substance P shows considerable alterations in transgenic mice as compared with their litter-mate, normal controls, producing divergent effects on hypothalamic catecholamine metabolism. The present findings confirm that transgenic mice overexpressing the bGH gene have marked neuroendocrine alterations as compared with their normal litter mates.