F. Casanueva

Opiates and their antagonists modulate luteinizing hormone acting outside the blood brain barrier

The effects of morphine methyl-iodide and naloxone methyl-bromide, two quaternary derivatives of morphine and naloxone, were evaluated on the modulation of luteinizing hormone secretion in intact and gonadectomized rats. Quaternary compounds are effective in modulating LH release, indicating a site outside the blood brain barrier for their action. More precisely, the median eminence and not the pituitary seems to be the site of action of opiates in modulating LH secretion, since the effect of the quaternary derivatives is abolished by surgical ablation of the median eminence.

Daily Fluctuations in the Activity of the Tuberoinfundibular GABAergic System and Plasma Prolactin Levels

In view of the role exerted by gamma-aminobutyric acid (GABA) in the control of prolactin (PRL) secretion the circadian periodicity of hypothalamo-pituitary GABAergic activity and PRL secretion was evaluated in adult male rats to ascertain if a meaningful correlation between biochemical and endocrine indices may be evidenced. Anterior pituitary and median eminence GABA concentrations peaked during the late afternoon hours (18.00 h), while the glutamic acid decarboxylase activity reached higher concentrations at 15.00 h. Plasma PRL presented two circadian surges at 15.00 h and at midnight. Although the changes of GABA in the hypothalamo-pituitary complex and the PRL surges did not show a close temporal relation, the possibility may be considered that GABA circadian changes occurred as a delayed response to PRL circadian surges. However, it cannot be excluded that changes in the biochemical indices could be related to other neuroendocrine events.

Regulation of prolactin secretion during suckling: involvement of the hypothalamo-pituitary GABAergic system

Previous results demonstrated that GABA exerts a dual control on PRL secretion, one excitatory mediated in part by the impairment of the tubero-infundibular dopaminergic (TIDA) system function, the other inhibitory occurring at the level of the anterior pituitary (AP), where 3H-GABA and 3H-Muscimol (3H-M) recognition sites have been described. This report provides evidence for a physiological role of the tubero-infundibular GABAergic system (TI-GABA) on PRL secretion in the rat. In lactating rats separated for 4 h from their pups reinstitution of suckling for different periods resulted in an increase either in glutamic acid decarboxylase (GAD) activity in the mediobasal hypothalamus (MBH) or in AP-GABA content. Dynamic changes of the GABAergic function in the MBH-AP system seemed to have a certain degree of specificity because suckling did not affect GAD activity in the caudate nucleus. In lactating rats 2, 4, 8 and 24 h after removal of the offsprings AP-GABA concentrations and plasma PRL titers significantly decreased with respect to values present in rats never separated from their pups. Since it has been demonstrated that the PRL lowering effect of GABA is a receptor-mediated event, we have investigated the plasticity of AP-GABA receptors during suckling. The inhibitory action of GABA seems to be mediated mainly by the activation of the high affinity binding sites. This proposition is supported by the fact that in lactating rats, where only the high affinity receptor population is present, M was still able to decrease significantly plasma PRL concentrations. These results indicate that the MBH-AP GABAergic system could play a role on PRL secretion, being involved in mechanisms which dampens PRL output during continuous suckling stimulation.

PROLACTIN AND GROWTH HORMONE-RELEASING EFFECTS OF ENKEPHALINS

Publisher Summary This chapter discusses prolactin and growth hormone-releasing effects of enkephalins. It reports studies performed to determine the mechanism whereby enkephalins induce PRL release in the rat and GH release in the dog and attempts to identify the location(s) in the CNS at which opiate receptors act to produce these effects. The studies allow the following conclusions. (1) A serotoninergic mechanism has to be considered in the PRL-releasing effect of enkephalins in rats, in addition to the well recognized inhibition of dopaminergic function. (2) Cholinergic and histaminergic links play a major role in mediating the GH-releasing effect of enkephalins in the dog, while no role has to be assigned to noradrenergic mediation. (3) The mediobasal hypothalamus is a critical area for the interaction between enkephalins and neurotransmitters for GH and PRL control, though for the latter, the possibility of a nonhypothalamic site of action may be envisaged.

Failure of different neuropharmacologic manipulations to trigger a paradoxical rise of growth hormone after glucose administration in the dog

Summary Several human pathological conditions, i.e., acromegaly, chronic liver disease, uremia, etc., are associated with a paradoxical rise in plasma growth hormone (GH) after glucose administration. Since in some of these conditions an altered brain neurotransmitter function is present or postulated to occur, it seemed worthwhile investigating whether in the dog a paradoxical rise in plasma GH after glucose may be elicited by abrupt modifications in brain function due to different neuropharmacologic manipulations. Neither stimulation of catecholamine, namely dopamine (DA), function by bromocriptine, nor its inhibition by drugs which block DA (pimozide), DA and norepinephrine (haloperidol), o(-adrenergic (phentolamine) or β-adrenergic (propranolol) receptors, was capable of modifying the glucose-induced GH pattern. Similarly ineffective was activation of brain serotoninergic function by previous administration of 5-hydroxytryptophan or its blockade by metergoline. In no instance a paradoxical rise of GH could be evoked following glucose administration. It is concluded that modifications in brain neurotransmitter function induced acutely cannot account for the deranged GH responsiveness to glucose present in several human pathological conditions.

DOPAMINE AGONIST AND ANTAGONIST DRUGS AND HYPOTHALAMIC PITUITARY DYSFUNCTION

It is now well established that a family of neuropeptides, the hypothalamic releasing and inhibiting or regulatory hormones, produced in neural cell bodies, regulate the secretory activity of the anterior pituitary (AP) gland. They are secreted at the level of the median eminence (ME) into the primary plexus of the hypophysial-portal blood vessels and are then vehicled to the AP cells, where they stimulate or inhibit the synthesis and release of AP hormones.