Prolactin actions

Mechanism of Action. Eew data are available that describe the effects of anaboHc steroids on protein metaboHsm even fewer data exist for assessment of direct effects of anaboHc steroids on Hpid metaboHsm in growing mminants. The lack of any consistent change in somatotropin, prolactin, insulin, or other metaboHc hormones (qv) in a total of 15 studies has been noted (1,38). 

Besides behavior and blood pressure, catecholamine neurons also have important roles in other brain functions. Regulation of neuroendocrine function is a well-known action of catecholamines for example, DA agonists reduce semm prolactin concentration, especially in conditions of hypersecretion. Ingestive behavior can be modulated by brain catecholamines, and some appetite-suppressing dmgs are beheved to act via catecholaminergic influences. Catecholamines also participate in regulation of body temperature. 

AOS responsiveness to hormonal influences is shown in the action of sodefrin on the lateral nasal sinus of newts (Cynops). The receptors in the accessory pocket are differentially affected by pituitary and ovarian hormones (Toyoda et al., 2000). The local EOG response to the pheromone (Fig. 5.1) was enhanced by the presence of prolactin or of estrogen alone. Receptor sensitivity increase is perhaps an alternate strategy to AOS receptor density increase several alternate routes of signal receptor adaptation (Fig. 7.1) have been hypothesised (Sorenson and Stacey, 1998). 

The administration of low doses of PCP to rodents induces hyperactivity and stereotypy (Chen et al. 1959 ). The observation that neuroleptics such as chlorpromazine, haloperidol, and pimozide, and adrenolytics such as alpha-methyl paratyrosine antagonize these behavioral effects of PCP suggests that they are mediated by facilitation of central dopaminergic neurotransmission (Murray and Horita 1979). The actions of PCP on central dopaminergic neurotransmission may be similar to amphetamine. A dose of PCP (2.5 mg/kg) in rats, which has no effects when given alone, enhances the behavioral effects of 1 and 3 mg/kg of d-amphetamine (Balster and Chait 1978). PCP, like dopamine, has also been shown to suppress plasma prolactin (Bayorh et al. 1983). However, the firm establishment of an excl usive relationship between dopamine neuro-transmission and PCP effects is difficult because of the prominent interactions of this drug with other neurotransmitter systems. 

The answer is d. (Hardman, pp 1371-13720 High prolactin levels in the serum result in amenorrhea, for reasons that are not known. Bromocriptine inhibits prolactin secretion through its dopaminergic action This compound, a semisynthetic ergot derivative, appears to be a dopamine receptor agonist. It is administered orally to the patient and, in most cases, menses occurs after a month of therapy. 

Pinilla L, Gonzalez LC, Tena-Sempere M, Aguilar E (2001) Evidence for an estrogenlike action of raloxifene upon the hypothalamic-pituitary unit raloxifene inhibits luteinizing hormone secretion and stimulates prolactin secretion in ovariectomized female rats. Neurosci Lett 311 149-152... 

Weisner JB, Koeng JI, Krulich L, Moss RL (1984) Site of action for -endorphin-induced changes in plasma luteinizing hormone and prolactin in the ovariectomized rat. Life Sci 34 1463-1473... 

Yin P, Kawashima K, Arita J (2002) Direct actions of estradiol on the anterior pituitary gland are required for hypothalamus-dependentlactotrope proliferation and secretory surges of luteinizing hormone but not of prolactin in female rats. Neuroendocrinology... 

Nickel ions have been shown to depress the in vivo and in vitro release of prolactin [336], while the release of growth hormone was stimulated, and only at relatively high ion concentrations. Hyperglycemia occurs in rats following intraperitoneal or intratracheal injections of NiCl2 [265, 337, 338], The mechanism of action of nickel appears to be inhibition of insulin release this inhibition could be related to the extremely high concentration of nickel found in the pituitary and the effect on the secretion of the pituitary hormones (growth hormone and adrenocorticotropic hormone). 

In order to review these putative relationships it is first useful to define a subset of well-characterized hormones and neurotransmitters that have been implicated in behavior. The chemicals selected for discussion here are among those for which a robust relationship with behavior has been proposed, including steroids (estrogens, progestins, androgens and glucocorticoids), proteins (prolactin) and the neuropeptides (oxytocin and vasopressin). All of these chemicals may act as hormones, neurotransmitters and/or neuromodulators. In addition, to understand the action of these hormones, it is helpful to be familiar with some of the more common neurotransmitters (described below). Space does not permit a discussion of the behavioral effects of many additional compounds with endocrine or paracrine properties. 

Rettori V, Wenger T, Snyder G, Dalterio S, McCann SM. (1988). Hypothalamic action ofdelta-9-tetrahydrocannabinol to inhibit the release of prolactin and growth hormone in the rat. Neuroendocrinology. 47(6) 498-503. 

FIGURE 8.4 The Bronson model of priming pheromone actions in rodents. Chemical signaling between males and females constitutes a feedback mechanism that results in accelerated maturation and reproduction. This, in turn, permits the mice to adjust their reproduction and population size quickly to respond to environmental conditions such as sudden food abundance at harvest time. FSH, follicle-stimulating hormone LH, luteinizing hormone PRL, prolactin. Stimulation and inhibition are marked by - - and —, respectively. (From Bronson and Coquelin, 1980.)... 

Bromocriptine (Parl el) [Antiparkinsonian Agent/Dopamine Receptor Agonist] Uses Parkin on Dz, hyperprolactinemia, acromegaly, pituitary tumors Action Direct-acting on the striatal dopamine receptors X prolactin secretion Dose Initial, 1.25 mg PO bid titrate to effect, w/ food Caution [B, ] Contra Severe ischemic heart Dz or PVD Disp Tabs, caps SE X BP, Raynaud phenomenon (vasospastic disorder resulting in discoloration of the fmgers/toes), dizziness, N, hallucinations Interactions T Effects W/ erythromycin, fluvoxamine, nefazodone, sympathomimetics, antihypertensives X effects W/ phenothiazines, antipsychotics EMS Monitor BP may cause intolerance to EtOH OD May cause NA, severe hypotension give IV fluids symptomatic and supportive... 

All antipsychotics except clozapine and perhaps olanzapine produce hyperprolactinemia by removing the inhibitory actions of dopamine on prolactin secretion. This results in amenorrhea, galactorrhea, and infertility in women and in loss of libido and impotence in men. Inhibition of the release of follicle-stimulating and luteinizing hormones may also play a role. In addition, weight gain is common, and food intake must be monitored. 

Mechanism of Action A dopamine agonist that directly stimulates dopamine receptors in the corpus striatum and inhibits prolactin secretion. Also suppresses secretion of growth hormone. Therapeutic Effect Improves symptoms of parkinsonism, suppresses galactorrhea, and reduces serum growth hormone concentrations in acromegaly. 

Mectianism of Action Agonist at dopamine Dj receptors suppressing prolactin secretion. Therapeutic Effect Shrinks prolactinomas, restores gonadal function, improves symptoms of Parkinson s disease. 

Oxytocin (OT) is a nonapeptide in which six amino acids form a ring closed by a disulfide bridge, while the ring itself forms an antiparallel pleated sheet. The tail portion of the peptide, composed of Pro-Leu-Gly-NHj, is also rigidly held in a folded conformation. Oxytocin causes the powerful contraction of some smooth muscles and plays a vital role in milk ejection (not to be confused with milk secretion, which is regulated by prolactin). It also has uterotonic action, contracting the muscles of the uterus, and is therefore used clinically to induce childbirth. 

It is a peptide containing 14 amino acids and inhibits the release of growth hormone, TSH and prolactin from the pituitary and insulin and glucagon in pancreas. It has a very short plasma half-life. Because of its shorter duration of action and lack of specificity in inhibiting only GH secretion, its use in the treatment of acromegaly is limited. 

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