Differential effects of prepubertal chronic oestrogen treatment on the synthesis of noradrenaline in uterine myometrial and perivascular sympathetic nerves

Previous studies have shown that chronic administration of oestrogen to pre pubertal rats reduces the total content of noradrenaline in the uterine hor n, abolishes myometrial noradrenergic innervation and reduces noradrenaline -fluorescence intensity of intrauterine perivascular nerve fibres. The mech anisms underlying these changes are not known. In the present study we have analysed the effects of prepubertal chronic oestrogen treatment on the syn thesis of noradrenaline in the rat uterine sympathetic nerves using biochem ical and immunohistochemical approaches. Tyrosine hydroxylase activity was evaluated biochemically, by measuring the in vivo accumulation of dihydroxy phenylalanine (DOPA) in the presence of a DOPA-decarboxylase inhibitor. In addition, nerve fibres were visualised immunohistochemically using antibodi es against tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (D beta H) and the general marker protein gene product 9.5 (PGP 9.5). After chronic oe strogen treatment, the total content of noradrenaline of the uterine horn w as reduced, whereas the total content of DOPA was increased. In controls, T H-immunoreactive, D beta H-immunoreactive and PGP 9.5-immunoreactive nerve fibres were distributed in both the circular and longitudinal myometrial la yers and in the blood vessels of the intra-myometrial region. After chronic oestrogen treatment the only fibres recognised by the three antibodies wer e those associated with the blood vessels, but no myometrial-associated fib res could be recognised. These results suggest that noradrenaline synthesis is selectively reduced in myometrial-associated uterine sympathetic nerves , but is preserved in perivascular sympathetic nerves. The increased DOPA l evels measured after chronic exposure to oestrogen was interpreted as the c onsequence of the substantial increase in size and number of blood vessels observed in the uterus of oestrogen-treated animals. A possible neurodegene rative effect of oestrogen on myometrial sympathetic fibres is discussed. ( C) 1999 Published by Elsevier Science Ltd on behalf of ISDN. All rights res erved.