Steven W. J. Lamberts

Studies on the Mechanism of the GABA-Mediated Inhibition of Prolactin Secretion

Summary GABA has a direct inhibiting effect on prolactin release by the pituitary in vitro and this effect is not blocked by coin-cubation with the specific GABA-receptor antagonist picrotoxin. GABA appears to be at least 100-fold less potent than dopamine as an inhibitor of prolactin secretion. Systemic administration of GABA did not affect basal serum prolactin levels, but inhibited the 5-hydroxytryptophan-induced secretion of prolactin. It is concluded that the direct effect of GABA on prolactin secretion by the pituitary is not mediated by well-defined neurotransmitter mechanisms.

Metergoline and Other Peipheral Serotonin Antagonists Inhibit Prolactin Secretion through Mechanisms Unrelated to Serotonin

Summary The mechanism through which metergoline and other peripheral serotonin receptor antagonists inhibit prolactin secretion was studied. Reserpine, an agent well known to deplete brain catecholamines and serotonin, increased the serum prolactin concentration in male rats. The concomitant injection metergoline completely prevented this increase in hormone level, suggesting that metergoline has a direct effect to inhibit secretion of the hormone. Direct addition of metergoline to pituitary glands incubated in vitro decrease the amount of prolactin secreted, confirming this suspicion. Haloperidol at the concentration used was without effect on prolactin secretion, but it completely blocked the metergoline-mediated inhibition of prolactin secretion. Similar effects were observed with methergine, a metabolite of methysergide, and with LSD. These data directly related to the finding that methysergide significantly decreased the in vivo prolactin secretion by a transplanted pituitary tumor. Simultaneous injection of haloperidol blocked the inhibitory action of methysergide. Similarly, the LSD-mediated inhibition of prolactin secretion in vitro was blocked by haloperidol. We conclude that the inhibiting action of metergoline and methysergide to inhibit prolactin secretion is exerted directly at the pituitary through the stimulation of a dopamine receptor.

Stimulation of Prolactin Release by the Bicarbonate Ion

Summary The bicarbonate ion was found to stimulate the in vitro release of RIA-PRL and [3H]PRL. Dopamine, as usual, inhibited the in vitro release of prolactin; however, the effects of the catecholamine were less evident at high molar concentrations of bicarbonate than at lower ones. Sodium ascorbate addition to high bicarbonate concentration increased the effectiveness of dopamine to inhibit prolactin. Ergocryptine decreased greatly the in vitro release of prolactin, and varying the bicarbonate concentration had no effect on this phenomenon. The results suggest that bicarbonate may interact with dopamine in regulating the physiological release of prolactin.

Reserpine inhibits rat anterior pituitary hormone secretion in vitro: Effects of prolactin and ACTH and ultrastructural observations

We measured [3H]prolactin ([3H]Prl) synthesis and secretion in female rat anterior hemipituitary glands incubated in vitro, and immunoassayable Prl secretion from dispersed anterior pituitary cells in a perfused column. Anterior pituitary glands which were incubated in 9 microM reserpine showed a marked inhibition of [3H]Prl secretion but no change in hormone synthesis, thus causing [3H]Prl accumulation within the gland. The same concentration of reserpine produced a similar effect in pituitary glands taken from rats depleted of dopamine with alpha-methyl-p-tyrosine. Reserpine inhibited Prl secretion from dispersed anterior pituitary cells with a gradual onset and prolonged duration. Thyrotropin-releasing hormone (TRH), but not dibutyryl cyclic AMP (dbcAMP), the calcium ionophore A23187 or excess Ca2+, stimulated both [3H]Prl and Prl secretion in the presence of reserpine. In contrast, neither basal nor vasopressin-stimulated ACTH (bio- and immunoassayable) secretion was inhibited by 9 microM reserpine. Ultrastructurally, pituitary glands incubated in reserpine had an increased content of Prl secretory granules. Reserpine thus selectively inhibited Prl secretion, secondarily causing accumulation of both measurable hormone and Prl secretory granules within the pituitary gland. We hypothesize that reserpine interrupted calcium-dependent mechanisms in the stimulus-secretion coupling process to inhibit Prl release.

Studies on the effect of cyproheptadine on growth hormone secretion.

Summary The administration of cypro-heptadine to female rats transiently decreased serum GH levels. Forty-five minutes after cyproheptadine injection, in vitro GH synthesis and release was significantly decreased. Although cyproheptadine decreased PRL release in vitro, the drug had no direct in vitro inhibitory effect on GH release. Cyproheptadine did not affect the secretion of GH and PRL from transplantable tumor MtTW15, although it inhibited the in vitro release of GH from dispersed tumor cells. Cyproheptadine had no effect on either tumor size or the biological actions produced by the tumor hormones.