Early unwanted effects of fluphenazine esters related to plasma fluphenazine concentrations in schizophrenic patients

Seven outpatients already receiving neuroleptic drugs by depot intramuscular injections were treated in two consecutive 3-week periods with 25 mg fluphenazine doses as enanthate and decanoate esters in a double-blind crossover study. They were assessed for incidence of akinesia, involuntary movement, autonomic disturbances and drowsiness, using a rating scale, and their blood pressures and pulse rates were recorded. Blood was collected for plasma fluphenazine and plasma prolactin assay. Additionally, a handwriting test was applied. A higher incidence of unwanted drug effects occurred when plasma fluphenazine concentrations were maximal, but this was not so with prolactin concentrations. No significant blood pressure changes occurred. Small increases in pulse rate and decreases in handwriting length occurred, but these changes were not associated with high fluphenazine levels.     

Effect of two dopamine agonists, TL-99 and 3-PPP, on prolactin secretion in the rat

TL-99 and 3-PPP, two putative dopamine autoreceptor agonists, effectively suppressed serum prolactin (PRL) concentrations in rats treated with -methyltyrosine. In addition, the secretion of PRL from anterior pituitary tissue under in vitro conditions was significantly inhibited by TL-99 and 3-PPP. These findings are supportive of the view that TL-99 and 3-PPP exert a dopamine agonist action at dopamine receptors in the anterior pituitary gland.     

Contractile effect of prolactin on guinea pig isolated ileum

Prolactin (PRL) at high concentrations contracted the guinea pig isolated ileum. The maximum response elicited by PRL was 44% of that of histamine-induced responses. There was no significant difference in potency between PRL preparations obtained from two different sources. PRL responses were nullified by denaturation or proteolytic digestion of the hormone. The contractile response was antagonised by atropine and potentiated by neostigmine, but unaffected by the prostaglandin antagonist SC-19220. The pA2 values of atropine against PRL and ACh were similar. Preincubation with morphine, which inhibits ACh release, produced slight inhibition of PRL-evoked contractions. Even high concentrations of PRL failed to produce any response in neostigmine-treated frog rectus muscle preparations. This suggests that PRL may produce contractions through a cholinergic mechanism involving muscarinic receptors. Enhanced gut motility reported earlier for hyperprolactinemic states may be attributed to this cholinomimetic effect of PRL on the intestinal tract.     

Superior cervical ganglionectomy differentially modifies median eminence and anterior and mediobasal hypothalamic GABA content in male rats: effects of hyperprolactinemia

This work was undertaken to analyze the changes in GABA concentrations in the anterior and mediobasal hypothalamus and in the median eminence after acute or chronic superior cervical ganglionectomy (SCGx), and whether high prolactin levels interfere with the effects of SCGx on GABA content. Acute but not chronic SCGx increased GABA content in all the areas studied, as compared to controls. The presence of a pituitary graft abolished the effects of acute SCGx in the median eminence and anterior hypothalamus, as compared to controls, but potentiated its effects in the mediobasal hypothalamus. Chronic SCGx increased GABA content in the mediobasal and anterior hypothalami, as compared to pituitary grafted controls. Acute SCGx decreased plasma prolactin and GH levels, but chronic surgery did not modify these hormone plasma levels. Acute SCGx increased plasma ACTH levels, whereas chronic SCGx did not modify them. Pituitary grafting increased circulating values of prolactin, ACTH and GH, as compared to controls. Acute SCGx did not modify plasma prolactin levels in grafted animals, although it increased plasma GH levels and decreased those of ACTH in this experimental group. Chronic SCGx further increased both plasma prolactin and GH levels, without modifying plasma ACTH levels. These results suggest that SCGx differentially modifies GABA content within the hypothalamus and median eminence. Induction of hyperprolactinemia in the neonatal age interferes with SCGx effects on both GABA content within the hypothalamus and median eminence and the secretory patterns of the pituitary hormones studied.     

A prospective,double-blind,randomized, placebo-controlled clinical trial of bromocriptin in clomiphene-resistant patients with polycystic ovary syndrome and normal prolactin level

Objective: The purpose of this study was to examine the effects of of bromocriptin combined with clomiphene citrate in clomiphene-resistant patients with polycystic ovary syndrome and normal prolactin level. Design: Prospective, double-blind, controlled study. Setting: University teaching hospital. Patients: One hundred polycystic ovary patients and normal prolactin (PRL) who were clomiphene citrate resistant. Interventions: Treatment group received 150 mg clomiphene citrate on days 5–9 and 7.5 mg bromocriptin continuously. Control group received the same protocol of clomiphene citrate combined with placebo. Main outcome measures: Hormonal status, follicular monitoring, ovulation rate. Results: Follicular development (follicular size greater than 15 mm) was observed in 12 (25.5%) and eight (15.1%) women in treatment and placebo group respectively (P=0.29). The serum prolactin level was within normal limits in all patients before treatment. After 3 and 6 months of treatment with bromocriptin, there was a significant decrease in serum level of prolactin (P=0.000001).No any significant differences was seen in ovulation, and serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), dehydroepiandrosterone sulfate (DHEAS), progesterone (P) between treatment and placebo group after treatment. Conclusions: The only significant effect of long-term bromocriptin therapy in clomiphene citrate resistant polycystic ovary women was to lower the serum prolactin concentration. It was also concluded that 10–15% of patients with polycystic ovaries experienced occasional ovulatory cycles and pregnancy whether or not they were on treatment. This work was performed at the Division of Infertility, Department of Obstetrics and Gynecology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.     

Effects of dopexamine,dobutamine or dopamine on prolactin and thyreotropin serum concentrations in high-risk surgical patients

Objectives Catecholamines are often used for optimisation of cardiac index and oxygen delivery in high-risk surgical patients; however, infusions of dopamine and dopexamine are associated with dose-dependent hypophysiotropic and thyreotropic properties. The objective was to compare endocrine effects of equipotent inotropic doses of dopexamine, dobutamine and dopamine on prolactin and thyreotropin release perioperatively.Design A prospective, randomised, blinded clinical trial.Setting Adult surgical intensive care unit in a university hospital.Patients Thirty male patients (ASA III) undergoing elective major abdominal surgery.Interventions Patients were randomised to receive dopexamine (DX, n=10), dobutamine (DO, n=10) or dopamine (DA, n=10) on the first postoperative day for 8 h.Measurements and results All patients received a catecholamine infusion in doses adjusted to increase cardiac index by 35% within the first hour. Blood samples were obtained and prolactin and thyreotropin serum concentrations were determined by radioimmunoassays. Mean doses of dopexamine, dobutamine and dopamine used were 0.73±0.27, 4.06±1.95 and 5.0±1.84 µg kg^–1min^–1, respectively. Cardiac index was increased by 36% (DX group), 38% (DO group) and 38% (DA group). Alterations of oxygen delivery and oxygen consumption were not significantly different between the study groups. Dopexamine and dobutamine had no hypophysiotropic effects. In contrast, dopamine suppressed prolactin and thyreotropin secretion with a maximal effect after 4 h. After dopamine withdrawal, a rebound release of prolactin and thyreotropin was observed.Conclusions In high-risk surgical patients dopexamine or dobutamine produced fewer effects on prolactin and thyreotropin serum concentrations in comparison with DA when used in equivalent dosages.     

Thyroid hormone, glucocorticoids, and prolactin at the nexus of physiology, reproduction, and toxicology

A symposium at the 2003 Annual Meeting of the Society of Toxicology brought together an expert group of endocrinologists to review how non-reproductive hormones can affect the endocrine system. This publication captures the essence of those presentations. Paul Cooke and Denise Holsberger recapitulate the evidence of how thyroid hormones affect male and female reproduction, and reproductive development. Ray Witorsch summarizes the many effects of glucocorticoids on the reproductive system. Finally, Paul Sylvester reviews the mechanism of action of prolactin, and reminds us that this ancient hormone has many functions beyond lactation.     

Glandular kallikreins in the teleost Cyprinus carpio: tissue distribution,possible involvement in prolactin processing,and effect of 17 beta-estradiol in vivo

We examined glandular kallikrein (GK), a putative prolactin processing protease, in the teleost Cyprinus carpio. When employing an anti-Centropristis striata GK antibody proteins of 39 kDa in muscle, 52 kDa in gill, 52 kDa in kidney, and two proteins of 46 and 72 kDa in pituitary gland were detected. Immunoreactive kallikreins were recognized in intermuscle cell tissue, epithelial gill cells, apical region of tubular cells, and prolactin producing lactotrophs in pituitary gland, suggesting a osmoregulatory role for this enzyme. We found three prolactin (PRL) variants using anti-tilapia PRL antibodies, in pituitary gland 23 and 16 kDa, and in plasma 23 and 22 kDa forms. Clearly co-localization of GK and PRL in lactotrophs could be demonstrated. In winter-acclimatized male carp, where the pituitary PRL level is low, 17beta-estradiol treatment increased PRL but not GK immunoreactivity. In contrast to GK and PRL co-regulation by estrogen in mammalian pituitary gland, no similar effect on immunoreactive PRL and GK was observed in the ichtyc pituitary. No changes in GK immunostaining occurred in gill or muscle tissue in response to estrogen treatment. These results, taken with the observation of significantly increased GK immunoreactivity in the apical region of kidney tubular cells in estrogen treated male carp, indicate that the regulation of GK expression in pituitary and kidney could be different in fish with respect to mammals.