Loss of Hypothalamic Dopaminergic Control of Prolactin Secretion in the Hyperprolactinaemic Rat

Abstract

The possibility that chronic hyperprolactinaemia results in loss of the ability of hypothalamic dopamine activity to inhibit prolactin secretion was studied in rats. Two degrees of hyperprolactinaemia (moderate and gross) were induced in the animals following the chronic administration of two different doses of oestradiol valerate. In rats with high chronic serum prolactin concentrations (approximately 20 times normal) there was a profound increase in prolactin secretion following inhibition of brain dopamine (DA) synthesis by 3-iodo-L-tyrosine, indicating intact and highly active hypothalamic DA-inhibitory control of prolactin release. However, the degree of hypothalamic inhibition of prolactin release relative to normal controls was significantly reduced. In animals with grossly elevated chronic serum prolactin concentrations (approximately 100 times normal) a prolactin response to DA synthesis inhibition was absent despite a highly significant reduction in hypothalamic DA concentrations induced by 3-iodo-L-tyrosine. These observations show that chronic and gross hyperprolactinaemia in the rat results in loss of hypothalamic DA inhibitory control of prolactin secretion. The use of 3-iodo-L-tyrosine to block brain DA synthesis in these studies has provided significant new data relating to prolactin control in hyperprolactinaemic states and indicates that this compound could be a useful clinical tool in the study of human hyperprolactinaemia.

Hypothalamic Monoaminergic Activity and Pituitary Function in Male Rats with Estrogen-Induced Pituitary Hyperplasia

“…Numerous studies have shown that PRL and PRL-releasing drugs stimulate the release of DA into the hypophysial portal blood and that these sub stances stimulate turnover of tuberoinfundibular DA neu rons [2,7,14,16,34,36,46]. The stimulatory effect of estra diol on DA release may be the result of the elevation in serum PRL and the subsequent positive feedback of PRL on DA release.…”

“…31], suggesting a pituitary site of action. High estrogen doses have also been shown to increase hypothalamic content of PRL-releasing factor activity [28], suppress tuberoinfundi bular dopaminergic activity [5,6,12,13,32] and structurally alter the hypothalamus [3,32], In contrast, other reports have shown enhanced hypothalamic dopaminergic activity in estrogen-treated animals [7,9,14,16,34,36]. The role of serotonin (5-HT) in estrogen-induced pituitary hyperplasia is even less clearly defined [4], Acute elevation of PRL by estrogen enhanced 5-HT neurotransmission in the medial…”

Different Acute Effects of the Tyrosine Hydroxylase Inhibitors a-Methyl-p-Tyrosine and 3-Iodo-L-Tyrosine on Hypothalamic Noradrenaline Activity and Adrenocorticotrophin Release in the Rat

“…The doses used were the same as are commonly used to inhibit tyrosine hydroxylase activity (Scapagnini et at. 1970;Lemmer and Berger 1978;Smythe et al 1982a).…”

“…The high accuracy of this technique and its simplicity has enabled assessment of neuronal activities of the brain monoamines in relation to concurrent pituitary hormone release in broad studies of neuroendocrine control mechanisms and these studies have resulted in previously unrecognized drug effects being revealed (Smythe et al 1982a(Smythe et al , 1982b(Smythe et al , 1982c(Smythe et al , 1983.…”

“…In the case of the use of a-MT, the overriding assumption has been that this compound is a specific inhibitor of tyrosine hydroxylase (Muller et al 1977) and its effects in stimulating ACTH were of importance in the development of the hypothesis that hypothalamic NA exerted inhibitory control over ACTH release (Muller et al 1977). 3-Iodo-L-tyrosine is another potent inhibitor of tyrosine 0004-9417/83/050519$02.00 hydroxylase (Udenfriend et al 1965) which we have used to inhibit DA synthesis in several studies (see Smythe et al 1982a). While MIT is a more potent tyrosine hydroxylase inhibitor than a-MT (Udenfriend et al 1965), in no investigation using MIT have we been able to observe any acute stimulation of ACTH such as had been shown for a-MT (Scapagnini et al 1970).…”