Prolactin effect

Unusually low rate of side effects Little EP or prolactin effects... 

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). 

The class III cytokine receptor family includes two TNE receptors, the low affinity NGE receptor and 7-ceU surface recognition sites that appear to play a role in proliferation, apoptosis, and immunodeficiency. TNE-a (- 17, 000 protein) is produced by astrocytes and microglia and can induce fever, induce slow-wave sleep, reduce feeding, stimulate prostaglandin synthesis, stimulate corticotrophin-releasing factor and prolactin secretion, and reduce thyroid hormone secretion. TNE-a stimulates IL-1 release, is cytotoxic to oligodendrocytes, and reduces myelination this has been impHcated in multiple sclerosis and encephalomyelitis. Astrocyte TNE-a receptors mediate effects on IL-6 expression and augment astrocytic expression of MHC in response to other stimulants such as lEN-y. 

Prolactin is peptide hormone secreted by the pituitary gland. It acts on prolactin receptors in breast tissue where it stimulates production of casein and lactalbu-min. It also acts on the testes and ovaries to inhibit the effects of gonadotrophins. Since the secretion of prolactin is under tonic dopaminergic inhibition by the hypothalamus, dopamine D2-receptor antagonists... 

No effect on prolactin release in normal subjects, but diminishes increased prolactin levels in acromegaly... 

Takahara J, Yunoki S, Yakushiji W, et ah Stimulatory effects of gamma-hydroxybutyric acid on growth hormone and prolactin release in humans. J Clin Endocrinol Metab 44 1014-1017, 1977... 

Those for the D2 receptor (e.g. bromocriptine) have a particular value in the treatment of Parkinson s disease by reproducing the effects of the dopamine lost through degeneration of the nigrostriatal tract (Chapter 15). They are also used to reduce the undesirable effects of prolactinaemia (high plasma prolactin), such as amenorrhoea and galactorrhoea. 

DA antagonists are anti-emetic, elevate plasma prolactin and have major motor and behavioural effects. Thus DA must be involved in the initiation of vomiting, the secretion of prolactin and control of motor and behavioural activity. Its role in emesis and as the prolactin release inhibitory factor have been adequately covered above. Its motor and behavioural function will now be considered. 

Importantly, they achieve this without inducing extrapyramidal side-effects or increasing prolactin secretion, which are real problems with neuroleptics. These results have been borne out by preliminary clinical trials of buspirone, used in combination with neuroleptics, and several novel S-HTja agonists (e.g. BSF 190555) are currently under development for this clinical application (Meltzer 1999). 

Nevertheless it must also be expected that anything which increases DA function not only controls extrapyramidal function but also reproduces the other central effects of DA i.e. vomiting, a reduction in prolactin secretion and some psychotic manifestations. In excess it may also cause dyskinesias. Despite these problems, the therapy of PD is one of the success stories of neurology. 

Bronson F. and Maruniak J.A. (1976). Differential effects of male stimuli on follicle stimulating hormone, luteinising hormone and prolactin secretion in prepubertal female mice. Endocrinology 98, 1101-1108. 

Ferkin M., Sorokin E. and Johnston R.E. (1997). Effect of prolactin on the attractiveness of male odors to females in Meadow Voles independance and additive effects with testosterone. Horn Behav 31, 55-63. 

Li C., Kaba H. and Seto K. (1994). Effective induction of pregnancy block by electrical-stimulation of the mouse accessory olfactory-bulb coincident with prolactin surges. Neurosci Lett 176, 5-8. 

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. 

If PCP produces its multitude of effects by activating PCP (sigma) receptors, then chronic exposure to agonists should elicit the development of tolerance. Tolerance to plasma prolactin suppression by PCP is observed in rats following daily administration for 28 days (Quirion et al. 1982). Chronic PCP treatment has been also shown to reduce the number of PCP sites (receptors) in rodent brains (Quiriun et al. 1983). Behavioral studies have documented the development of tolerance to and dependence on PCP (Balster and Woolverton 1980 Flint and Ho 1980). A tolerance syndrome develops in humans, in which the user is compelled to increase his intake of drug (Jain et al. 1977). 

Low-dose dopamine is not without adverse reactions and most studies have failed to evaluate its potential toxicities. Adverse reactions that may be associated with low-dose dopamine include tachycardia, arrhythmias, myocardial ischemia, depressed respiratory drive, and gut ischemia. Low-dose dopamine has also been postulated to impair resistance to infection through a reduction in prolactin concentrations.21 Furthermore, significant overlap in receptor activation occurs. Therefore, doses considered to activate only dopamine receptors may increase cardiac output and blood pressure through dopamine s effect on 3- or a-adrenergic receptors. 

Bromocriptine directly binds to the D2 receptors on the lac-totroph cells to exert its effect. Bromocriptine normalizes prolactin level, restores menstrual cycles, and reduces tumor size in approximately 90% of patients.49 Adverse effects such as nausea, dizziness, and orthostatic hypotension often limit 5% to 10% of patients from continuing treatment. Thus, start bromocriptine at a low dose (e.g., 0.625-1.25 mg) at bedtime... 

---