The Role of Serotonin and Dopamine in Hypothalamic‐pituitary Function

The induction of hyperprolactinaemia in the male rat following chronic oestrogen administration over 3 months was shown to result in a highly significant reduction in hypothalamic dopamine (DA) concentration as well as significant reductions in hypothalamic noradrenaline (NA) and serotonin (5-HT). Significant increases in hypothalamic DA synthesis were found 4 days after a single dose of oestrogen but not after 3 months' chronic treatment. However, after the latter treatment there was a reduction in the ratio of the level of DA to its acidic metabolites in the hypothalami of the rats.When small doses of the ergot bromocriptlne were chronically administered to oestrogen-treated rats a significant return towards normal concentrations was noted for serum prolactin and the hypothalamic catecholamines but 5-HT was suppressed even further. An acute dose of bromocriptine given to rats which had been chronically administered oestrogen caused a complete reversal of hyperprolactinaemia and a small increase in hypothalamic DA levels.The suppressive effects of chronic oestrogen treatment on hypothalamic monoamines in intact rats was not observed in hypophysectomized rats. In hypophysectomized rats after chronic oestrogen treatment hypothalamic DA concentration was not significantly different from that of normal controls while both NA and 5-HT were significantly elevated.In this investigation oestrogen-induced hyperprolactinaemia was found to relate to hypothalamic DA but not to NA or 5-HT. In normal and oestrogen-treated rats there was found to ,be a highly significant correlation between serum prolactin and hypothalamic DA concentration. The data indicate that the reduction in hypothalamic DA is primarily due to the hyperprolactinaemia and not to a direct action of oestrogen on the brain.This study raises the possibility that reduced hypothalamic DA concentrations may be related to the degenerative hypothalamic lesions seen in chronically oestrogen-treated rats and that these lesions may be an effect of prolactin rather than oestrogen as proposed previously.

Section: Discussionsupporting

confidence: 80%

Oestrogen-Induced Hyperprolactinaemia in the Rat: Reduced Concentrations of Hypothalamic Dopamine and the Effects of Bromocriptine

Smythe¹,

Brandstater²

1980

“…Neither DA nor NA showed this effect. These findings support the proposed stimulatory role for 5-HT in GH secretory pathways (Smythe et al 1975;Smythe 1977) and provide evidence that 5-HT may also participate in TSH secretory mechanisms. The reduced GH secretion observed in the oestrogen-treated animals is consistent with the finding of reduced pituitary content of GH in rats treated chronically with high doses of oestradiol benzoate (Daughaday et al 1968).…”

Section: Discussionsupporting

confidence: 77%

Effects on the Secretion of Pituitary Growth Hormone, Thyroid Stimulating Hormone, Luteinizing Hormone and Follicle Stimulating Hormone in Rats Rendered Hyperprolactinaemic by Chronic Treatment with Oestrogen

Smythe¹,

Brandstater²,

Vining³

1981

The induction of hyperprolactinaemia in the male rat following chronic high-dose oestrogen administration over 3 months was associated With a significant inhibition of the secretion of growth hormone (OH) (P < 0·02) thyroid stimulating hormone (TSH) (P < 0·0025), luteinizing hormone (LH) and follicle stimulating hormone (FSH) (both P < 0·01). Acute, but not chronic, administration of bromocriptine (1 mg/kg) to these hyperprolactinaemic animals had the effect of normalizing the serum levels of GH and TSH but not those of LH or FSH. While the effects observed on GH, TSH, LH and FSH following induction of hyperprolactinaemia are likely to be consequential to brain actions of prolactin, the present data do not exclude the possibility of direct actions of oestrogen itself.

“…The biogenic aminesthought primarily to be involved in these mechanisms are the catecholamines dopamine and noradrenaline, and the indoleamine serotonin. However, the precise roles of the monoamines in specific neuroendocrine mechanisms remain controversial and unresolved (Smythe 1977). A lot of the data used to formulate hypotheses about the roles of the brain monoamines in the release of pituitary hormones have been derived by using drugs to alter the activity and concentrations of the brain monoamines and then observing the resultant effects on pituitary hormone release.…”

Section: Introductionmentioning

confidence: 99%

A Simple Procedure for the Assay of Brain Biogenic Amines by Selected-Ion Monitoring: Its Application to the Elucidation of the Mechanism of Prolactin Release Induced by 3-Iodo-L-Tyrosine

Smythe¹,

Brandstater²,

Bradshaw³

et al. 1979

A simple method for the assay of brain biogenic amines by selected-ion monitoring was applied to examination of the effects of 3-iodo-L-tyrosine on the hypothalamic-median eminence concentrations of dopamine, noradrenaline and serotonin in the rat. Thirty minutes after its administration iodotyrosine (50 mg/kg) caused a highly significant (P < 0·0005) rise in serum prolactin and a highly significant (P < 0·0025) fall in the concentration of dopamine in the hypothalamus and median eminence where the levels reached 50% of control levels. Less marked but significant falls were also observed in the hypothalmic (P < 0·05) and median eminence (P < 0·0025) concentrations of noradrenaline after iodotyrosine administration. Serotonin concentration was significantly reduced (P < 0·025) in the median eminence but not in the hypothalamus after iodotyrosine administration.These findings suggest that iodotyrosine exerts its prolactin stimulating effect by blockage of dopamine synthesis rather than by receptor blockade.