Adrenergic and Dopaminergic Modulation of Growth Hormone and Prolactin Secretion in Normal and Tumor-Bearing Human Pituitaries in Monolayer Culture*

Adrenergic and dopaminergic agonists administered in vivo stimulate GH secretion and inhibit PRL release. To investigate the direct effect of these agents on GH and PRL secretion from normal and tumor-bearing human pituitaries, they were added to monolayer cultures of surgically obtained pituitary tissue from patients with metastatic breast carcinoma, prolactinoma, and acromegaly. In the normal pituitary cultures, dopamine (10-5 M) significantly inhibited the mean GH secretory rate by 30%, dopamine (10-6 M) by 25%, apomorphine (10-5 M) by 56%, bromocriptine (10-5 M) by 74%, and norepinephrine (10-5 M) by 49%. PRL secretion in the normal pituitary cultures was also significantly inhibited by 10-5 M concentrations of dopamine, apomorphine, bromocriptine, norepinephrine, and epinephrine. These effects of dopamine and apomorphine on PRL secretion were inhibited by dopaminergic blockade with haloperidol and pimozide. In the acromegalic pituitary tumor cultures, the GH responses to dopamine were variable. In two of the four tumors, dopamine caused significant inhibition of GH secretion. This effect of dopamine on GH secretion was inhibited by dopaminergic blockade with haloperidol. In tissue from the other adenomas, dopamine (10-5 M) significantly stimulated GH secretion from one tumor, but had no effect on GH release from the other. GH secretory responses to L-dopa, norepinephrine, and epinephrine were also variable in the acromegalic adenomas. Differing responses to dopamine were also noted in patients with prolactinomas. One patient with a prolactinoma had normal suppression of serum PRL levels with a 0.04 μg/kg-min iv dopamine infusion. This correlated with the normal dopamineinduced inhibition of PRL secretion observed in monolayer culture of this tissue. In contrast, another prolactinoma subject demonstrated decreased sensitivity to iv dopamine. In monolayer culture of this tumor tissue, PRL secretion was similarly resistant to the suppressive effects of dopamine as well as those of apomorphine and bromocriptine. This study demonstrates that adrenergic and dopaminergic agonists directly inhibit normal human pituitary PRL and GH secretion. These findings are in contrast to the known in vivo GH stimulatory effect of these agents in man, which suggests that dopaminergically induced GH release may be mediated via the hypothalamus or higher central nervous system centers. In addition, dopaminergic defects exist in the adenomatous somatotrophs and lactotrophs of some patients with pituitary tumors.