Loss of Central Nervous System Component of Dopaminergic Inhibition of Prolactin Secretion in Patients with Prolactin-Secreting Pituitary Tumors

Abstract

A B S T R A C T The administration of L-dopa suppresses prolactin (PRL) secretion in normal subjects and in patients with hyperprolactinemia, although it is not known whether this effect, which requires the conversion of dopa to dopamine, is mediated peripherally or through the central nervous system. To distinguish between these effects, 10 normal subjects (6 male, 4 female) and 8 patients with hyperprolactinemia associated with pituitary tumors were given L-dopa, 0.5 g alone, or 0.1 g after a 24-h pretreatment with carbidopa, 50 mg every 6 h, which produces peripheral dopa decarboxylase inhibition. Similar degrees of PRL suppression were observed in normal subjects (basal plasma PRL 13+2 ng/ml) after L-dopa alone (48±+4%) and after L-dopa plus carbidopa (58+6%). In patients with pituitary tumors and elevated plasma PRL (73+14 ng/ml), L-dopa alone led to PRL suppression comparable with that in normal subjects (47±+6%). However, L-dopa plus carbidopa resulted in only minimal suppression of plasma PRL (19+4%) which was significantly less than after L-dopa alone (P < 0.001). Urinary homovanillic acid excretion, which reflected peripheral dopa decarboxylation was similar in controls and tumor patients after L-dopa both alone and after carbidopa pretreatment.

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

“…As previously suggested (Smythe and Brandstater 1980) these changes may be degenerative and be related to the neuronal lesions seen in the hypothalamic arcuate nucleus of rats after chronic E2 treatment (Brawer and Naftolin 1979). The loss of hypothalamic DA inhibitory control of prolactin secretion in the hyperprolactinaemic rat demonstrated in this investigation is in accord with similar findings in patients with prolactinsecreting tumors (Fine and Frohman 1978;Van Loon 1978).…”

“…These findings suggest the possibility that in the presence of pituitary tumors and marked hyperprolactinaemia there is reduced hypothalamic DA inhibitory control of prolactin secretion in the rat when, indeed, it would be anticipated that such inhibitory activity should be high due to the negative feedback function of prolactin itself. It is notable that such a situation with loss of hypothalamic DA inhibition of prolactin secretion seems to occur in humans with prolactin-secreting tumors (Fine and Frohman 1978).…”

Persistence of impaired PRL responses to sulpiride in patients with PRL secreting pituitary adenomas after successful hypophysectomy.

“…The inadequate PRL responses in PRL-noma seen after the hypophysectomy may be due to the reduced sensitivities of adenoma cells to the blocking effect of sulpiride on an inhibitory dopaminergic mechanism. We cannot, however, rule out the possibility that such inadequate responses depend more or less upon the hypothalamic dopaminergic abnormalities (Fine and Frohman 1978 …”

Influence of Pituitary Disease on Sexual Development and Functioning

“…create a state of secondary gonadal hormone insufficiency [13,14]. Adrenal steroids in high levels may suppress the reproductive axis by inhibiting GnRH and gonadotropin…”