Gamma-Aminobutyric Acid Is not Likely a Physiological Prolactin-Inhibiting Factor

Abstract

Basal plasma prolactin concentration is controlled by tonic inhibition. The major prolactin-inhibiting factor (PIF) is believed to be dopamine. Factors other than dopamine have also been suggested as possible physiological PIF. One of the major candidates for the nondopaminergic PIF is considered to be gamma-aminobutyric acid (GABA). We have carefully examined the possible physiological role of GABA by monitoring, at every 2 min, the circulating prolactin concentration after GABA administration, in conscious freely moving rats. GABA (0.1 or 1 g/kg) had no significant direct effect on plasma prolactin in rats in which the dopaminergic receptors were completely blocked by pimozide, nor in hypophysectomized rats in which a pituitary had been grafted under the kidney capsule and was therefore removed from any hypothalamic influence. The effects of bicuculline, a GABA-receptor-blocking agent, was examined in order to find out whether a tonic inhibition is exerted by GABA after elimination of tonic dopaminergic inhibition on prolactin secretion. The pimozide-treated rat in which the dopaminergic tone is completely eliminated did not show any prominent elevation of plasma prolactin concentration after bicuculline (300 µg/kg) administration. However, GABA did have an inhibitory effect in a primary pituitary cell monolayer culture system. Therefore, we conclude that GABA does not play a significant role as a physiological PIF and that the inhibitory effect of GABA in vitro is of a pharmacological nature.

Hypothalamic Prolactin Receptor Messenger Ribonucleic Acid Levels, Prolactin Signaling, and Hyperprolactinemic Inhibition of Pulsatile Luteinizing Hormone Secretion Are Dependent on Estradiol

“…The effects of ethanolamine-O-sulfate on the hypothalamic and anterior pituitary GABA concentration and prolactin secretion occur much earlier than the increase of GABA concentration in the peripheral plasma, indicating that circulating GABA does not play a functional role in the control of prolactin secretion (56). It should be mentioned, however, that the physiological importance of GABA in the hypophysial portal blood has been subsequently challenged by others (1247,1619). Nevertheless, the physiological role of GABA in regulating prolactin secretion is further supported by a close temporal relation between daily fluctuations in the activity of the tuberoinfundibular GABAergic system and the circadian prolactin surges (293).…”

Regulation of prolactin secretion: Dopamine is the prolactin‐release inhibiting factor (PIF), but also plays a role as a releasing factor (PRF)

“…However, close examination of the effects of GABA showed that it is not a physiological PIF . GABA and its agonists inhibit prolactin release in a dose-related manner in vitro (Enjalbert et al, 1979;Schally et al 1977;Shin et al, 1984), but a GABA agonist or antagonist does not inhibit or stimulate, respectively, prolactin release in conscious freely moving rats . GABA cannot be involved in this ether-induced prolactin release since GABA is ineffective on prolactin release in in vivo system.…”

The effects of the nonselective benzodiazepine lorazepam and the α2/α3 subunit‐selective GABAA receptor modulators AZD7325 and AZD6280 on plasma prolactin levels

“…GABA may directly inhibit the activity of the hypothalamic tuberoinfundibular dopaminergic pathway, with a resulting increase in prolactin secretion . It has also been reported that GABA exerts a dual control and can also have an inhibitory effect on prolactin release by acting at GABA receptors in the anterior pituitary gland, but this effect is less clear in vivo than in vitro. Only a few studies have evaluated the direct effects of GABAergic drugs on circulating basal prolactin levels in healthy subjects.…”