Increased Serum Prolactin Concentrations Research Articles

Lack of Relationships Between Serum Prolactin Concentrations and Classical Cardiovascular Risk Factors in Eastern Croatian Older Adults.

BackgroundRelationships between serum prolactin concentrations and various CV risk factors in older adults have rarely been assessed. The aim of this study was to examine the relationships between serum prolactin concentrations and CV risk factors in older patients with multiple CV risk factors.Material/MethodsThis case-control study included 92 patients, 50–89 years old (median, 69 years), with multiple CV risk factors. We used data from general practice electronic health records and biochemical laboratory tests. Patients were divided according to categories of CV risk factors.ResultsSerum prolactin concentrations were significantly higher in elderly people (≤65 vs. >65) and in men (70.65±58.02 vs. 150.82±114.05 mIU/L), as well as in patients with lower renal function (156.70±127.23 vs. 72.53±37.25 mIU/L, the bottom vs. top quartile of creatinine clearance), higher serum homocysteine and TSH concentrations, and in those who used NSAID and statins. Parameters indicating chronic inflammation (CRP) and renal function decline (creatinine clearance) were significantly and independently correlated with increased serum prolactin concentrations in multiple regression analysis.ConclusionsWhen assessing the relationships between prolactin and CV risk factors in older people with multiple CV risk factors, the effect of renal function decline and chronic inflammation should receive attention.

Effect of metoclopramide treatment of bitches during the first week of lactation on serum prolactin concentration, milk composition, and milk yield and on weight gain of their puppies.

OBJECTIVE To investigate effects of metoclopramide orally administered to healthy bitches on serum prolactin and milk lactose concentrations, gross energy, and dry matter content and on puppy weight gain during early lactation. ANIMALS 20 client-owned bitches and their 121 puppies. PROCEDURES 10 bitches received metoclopramide (0.2 mg/kg, PO, q 6 h for 6 days; treatment group) starting 10 to 24 hours after birth of the last puppy of the litter (day 0), and 10 bitches served as the control group. Blood and milk samples from all bitches were collected on days 0, 1, 2, 4, and 6. Milk samples for days 1 and 2 and days 4 and 6 were pooled because of small volume. Puppies were weighed twice daily. RESULTS Serum prolactin concentration increased significantly over time in both groups, and no treatment effect was detected. When day-to-day changes were analyzed, the prolactin concentration increased from day 0 to day 1 in the treatment group but not in the control group. Milk lactose concentration increased significantly and was higher in the treatment group than in the control group. Milk dry matter content was unchanged, whereas the time course for milk gross energy content differed significantly between treatment and control bitches. Puppy weight gain was not affected by metoclopramide treatment. CONCLUSIONS AND CLINICAL RELEVANCE Oral administration of metoclopramide to healthy bitches after parturition induced a transient increase in serum prolactin concentration and stimulated milk lactose production. It is likely bitches with insufficient or delayed milk production could benefit from metoclopramide treatment.

HSD17B1 expression induces inflammation-aided rupture of mammary gland myoepithelium.

Hydroxysteroid (17-beta) dehydrogenase type 1 (HSD17B1) converts low-active estrogen estrone to highly active estradiol. Estradiol is necessary for normal postpubertal mammary gland development; however, elevated estradiol levels increase mammary tumorigenesis. To investigate the significance of the human HSD17B1 enzyme in the mammary gland, transgenic mice universally overexpressing human HSD17B1 were used (HSD17B1TG mice). Mammary glands obtained from HSD17B1TG females at different ages were investigated for morphology and histology, and HSD17B1 activity and estrogen receptor activation in mammary gland tissue were assessed. To study the significance of HSD17B1 enzyme expression locally in mammary gland tissue, HSD17B1-expressing mammary epithelium was transplanted into cleared mammary fat pads of wild-type females, and the effects on mammary gland estradiol production, epithelial cells and the myoepithelium were investigated. HSD17B1TG females showed increased estrone to estradiol conversion and estrogen-response element-driven estrogen receptor signaling in mammary gland tissue, and they showed extensive lobuloalveolar development that was further enhanced by age along with an increase in serum prolactin concentrations. At old age, HSD17B1TG females developed mammary cancers. Mammary-restricted HSD17B1 expression induced lesions at the sites of ducts and alveoli, accompanied by peri- and intraductal inflammation and disruption of the myoepithelial cell layer. The lesions were shown to be estrogen dependent, as treatment with an antiestrogen, ICI 182,780, starting when lesions were already established reversed the phenotype. These data elucidate the ability of human HSD17B1 to enhance estrogen action in the mammary gland in vivo and indicate that HSD17B1 is a factor inducing phenotypic alterations associated with mammary tumorigenesis.

Differential diagnosis and management of abnormal uterine bleeding due to hyperprolactinemia

Abstract Abnormal uterine bleeding may be acute or chronic accounting for up to 30% of outpatient visits to gynecologists. Hyperprolactinemia is one of the most common endocrine disorders associated with ovulatory dysfunction that results in menstrual irregularities. Prior to initiating treatment, the various causes (physiologic, pathologic, pharmacologic, or idiopathic) of hyperprolactinemia must be elucidated. Prolactin is a stress hormone that increases in response to stressful conditions; therefore, while collecting samples it is necessary to reduce venipuncture stress. A thorough patient history and physical examination will help to identify the cause and to direct therapy. Imaging results must always be assessed along with a patient’s clinical history and biochemical parameters when a pituitary tumor is suspected. Magnetic resonance imaging is the method of choice for the diagnosis of microprolactinomas and macroprolactinomas in both initial assessment and follow-up. Several drugs may cause a significant increase in serum prolactin concentration. If clinically feasible, the drug should be discontinued; if this is not possible, it should be substituted with a drug of similar action that does not cause hyperprolactinemia. Prolactinomas are the most common cause of pituitary adenomas affecting women of fertile age leading to significant elevations in prolactin that warrant treatment. Idiopathic hyperprolactinemia may be observed in the presence of elevated serum prolactin levels and in the absence of any other recognized cause of increased prolactin secretion. Dopamine agonists are the mainstay of therapy in prolactinomas and symptomatic idiopathic hyperprolactinemia because they normalize serum prolactin, effectively shrink prolactinomas and normalize gonadal function (i.e. menstruation).

Clomipramine-induced serum prolactin as a marker for serotonin and dopamine turnover: results of an open label study

Central nervous system (CNS) monoamine deficits have been linked to a number of pathological conditions such as major depressive disorder. Individual biological variations in 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) might account for the variation in responses of neurotransmitter systems observed after the administration of clomipramine. The prolactin response to clomipramine has been widely used to assess CNS functioning. This open label study investigates the prolactin response induced by clomipramine in the plasma of healthy volunteers and whether it is related to changes in monoamine metabolites. The effects of clomipramine challenge on prolactin, 5-HIAA, HVA and MHPG were measured in 12 healthy volunteers. Samples were drawn directly before and 50min after clomipramine infusion. A statistically significant increase in serum prolactin concentrations was measured in women 50min after CMI infusion, but not in men. We found no significant increases in the serum monoamine metabolite concentrations 50min after CMI infusion. Changes in HVA and 5-HIAA correlated statistically significantly and positively with the amount of prolactin release in the whole sample. Furthermore, positive correlations were found between ∆(50-0 min) 5-HIAA and ∆(50-0 min) HVA, although we did not find a correlation between ∆(50-0 min) prolactin and ∆(50-0 min) MHPG after clomipramine challenge. The pronounced prolactin release in healthy adult women might indicate a higher physiological sensitivity. Correlations between intra-individual changes in HVA, 5-HIAA and serum prolactin might indicate a central nervous effect of clomipramine on monoamine turnover. We conclude that monoamine changes in relation to prolactin response after clomipramine challenge may be suitable for characterizing the relationship between central serotonergic and dopaminergic function.

Hyperprolactinemia and possibly related development of prolactinoma during amisulpride treatment; three cases

Schizophrenia is a chronic and debilitating psychotic mental disorder that affects about 1% of the world's population. Antipsychotic drugs are the mainstay of treatment in schizophrenia. Hyperprolactinemia, which is a common side effect of typical antipsychotics, is also associated with the use of some of the newer atypical agents. Antipsychotics may enhance prolactinoma growth as manifested by an increase in serum prolactin concentration. Prolactin-secreting pituitary adenomas possibly related with antipsychotics have been described in the literature. To our knowledge, this is the first series of cases showing a possible relation between pituitary adenomas and amisulpride treatment in patients with schizophrenia.

Effects of estrogen receptor subtype-selective agonists on autoimmune disease in lupus-prone NZB/NZW F1 mouse model

The specific roles of estrogen receptor (ER) subtypes α and β in mediating estrogen’s influences on lupus autoimmunity are unknown. Herein we found that ovariectomized NZB/NZW F1 mice treated with propyl pyrazole triol (ERα-selective agonist) had significantly shorter survival, earlier development of albuminuria, higher serum concentrations of total IgG and prolactin, increased serum levels of anti-DNA IgG3, IgG2a and IgG2b and decreased anti-DNA IgG1 level compared to vehicle controls. In contrast, diarylpropionitrile (ERβ-selective agonist) administration significantly decreased serum anti-DNA IgG2b level but did not significantly affect serum levels of other anti-DNA IgG subclasses, serum total IgG or prolactin concentration, mortality or the occurrence of albuminuria. These findings suggest that ERα activation plays the predominant and immunostimulatory role in estrogen-mediated modulation of lupus while ERβ activation appears to have a slightly immunosuppressive effect on this disease. ERα activation coincidentally increased serum prolactin concentrations and may accelerate lupus disease activity also through this mechanism.

Sexual dysfunction and antipsychotic treatment

Human sexual function is complex and affected in many different ways by schizophrenia and the antipsychotic drugs used in its treatment. The evaluation of the effects of antipsychotics on sexual function in patients with schizophrenia is also complex because the deleterious effects of conventional antipsychotics are superimposed on the effects of the disease itself. Although not extensively researched, sexual dysfunction seems to be frequent in patients with schizophrenia, especially in men. Sexual dysfunction appears, in significant part, to be a direct consequence of dopamine antagonism, combined with indirect effects due to increased serum prolactin concentration. Atypical antipsychotics have a number of potential advantages over standard agents with regard to their impact on sexual function. Clinical reports indicate that atypical antipsychotics are associated with a lower incidence of sexual adverse events than conventional antipsychotics and that there may also be important differences between them in this regard. For example, dose-related increases in prolactin concentrations occur with risperidone whereas olanzapine is associated with mild and transient increases in long-term treatment. Treatment with clozapine does not result in prolactin elevation and, like olanzapine, only transient increases occur with ziprasidone therapy, but the risk of agranulocytosis with clozapine restricts its use. Quetiapine has no more effect on serum prolactin than placebo across its full dose range. Together with its low frequency of reproductive or hormonal side effects and a low incidence of extrapyramidal symptoms, the tolerability profile of quetiapine may be particularly beneficial for many patients. Sexual dysfunction can be an important source of distress to patients and adversely affects compliance, and is one of the factors that must be taken into account when selecting treatment.

Fasting stimulates tuberoinfundibular dopaminergic neuronal activity and inhibits prolactin secretion in oestrogen-primed ovariectomized rats: involvement of orexin A and neuropeptide Y.

Fasting up-regulates central orexigenic systems including orexin A and neuropeptide Y (NPY) and it also inhibits the secretion of prolactin. We hypothesized that fasting may act through orexin A and NPY to influence tuberoinfundibular dopaminergic (TIDA) neurones, the major regulator of prolactin secretion. The effects of orexin A and NPY on TIDA neuronal activity and prolactin secretion were determined in oestrogen-primed ovariectomized rats, and the effects of fasting and the involvement of orexin A and NPY were tested. Orexin A, NPY and its analogs were administered through preimplanted intracerebroventricular (i.c.v.) cannulae. TIDA neuronal activity was determined by measuring concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC) or 3,4-dihydroxyphenylalanine in the median eminence. i.c.v. injection of NPY (10 microg) or orexin A (1 microg) concomitantly increased median eminence DOPAC and decreased serum prolactin concentrations. The effect of NPY was mimicked by a Y1 receptor agonist at lower doses (0.1 and 1 microg) and no additive effect was observed when orexin A and the Y1 agaonist were coadministered. Moreover, a Y1 receptor antagonist, BIBP, not only blocked the effect of Y1 agaonist, but also that of orexin A. Treatment with BIBP alone decreased median eminence DOPAC and increased serum prolactin concentrations, indicating that endogenous NPY may play a role. Moreover, fasting for 48 h significantly increased TIDA neuronal activity, both in the morning and afternoon, and the effect was reversed by treatment with either BIBP or an antibody against orexin A. The findings support our hypothesis that fasting stimulates TIDA neuronal activity and inhibits prolactin secretion through up-regulated central orexin A and NPY systems.

Increased Hypothalamic Dopaminergic Tone Only in Early Parous Women with either Malignant or Benign Breast Tumors

To investigate whether the serum prolactin (PRL) response to a dopamine antagonist was different in nonobese, euthyroid women with malignant or benign breast tumors in comparison with healthy women, considering their age at first full-term pregnancy or their nulliparity. Serum PRL concentrations before and 60, 90, and 120 minutes after oral administration of metoclopramide (10 mg) were studied in 122 nonobese, nonsmoking, euthyroid women: 28 who had invasive breast cancer, stage I or II (group 1), 34 who had benign breast disease (group 2), and 60 who were clinically healthy (group 3). These three main groups were subdivided into early and late parous women (< or = 25 and >25 years, respectively) and nulliparous women, and the menopausal status was also considered. Early parous women with invasive breast cancer (both premenopausal and postmenopausal) and early parous premenopausal women with benign breast disease had significantly higher serum PRL concentrations in response to administration of metoclopramide (P<0.05) and a greater area under the PRL curve (P<0.05) than those observed in early parous healthy women. No other significant differences in the serum PRL response were noted between or within groups. The results of this study suggest the existence of an increased hypothalamic dopaminergic tone in early parous women but not in late parous or nulliparous women with malignant or benign breast tumors in comparison with similar healthy women. This finding may represent an adaptive protective mechanism attempting to prevent persistently increased serum PRL concentrations, a factor that could adversely affect the clinical evolution of the disease.

Elevated Levels of Serum Prolactin in Patients with Advanced Multiple Myeloma

Background and Objective: The role of prolactin in immunoregulation and normal hemopoiesis is well known. However, prolactin also seems to be involved in the pathomechanism of malignancies and autoimmune diseases. Elevated serum prolactin levels were reported in patients with malignant lymphoma, colon and breast carcinoma, systemic lupus erythematosus and rheumatoid arthritis. Recently we demonstrated prolactin immunostaining in bone marrow cells of patients with multiple myeloma. Design and Methods: Serum prolactin levels of 56 patients with multiple myeloma, as well as serum β₂-microglobulin, and interleukin-6 concentrations were determined in this study. Results: Patients with advanced disease showed a significant increase in serum prolactin concentration, while patients with a clinical stage of I and II, and also control patients had normal values. The concentration of serum β₂-microglobulin and interleukin-6 changed in parallel with that of serum prolactin in patients with multiple myeloma. Determining serum prolactin levels several times during the disease process in a given patient clearly showed that the prolactin concentration was increasing during the disease progression. Interpretation and Conclusions: Our results indicate a role of prolactin in disease progression in multiple myeloma.

Effects of dopamine d2 receptor agonists in a pituitary transplantation-induced hyperprolactinaemia/anovulation model in rats.

1. In the present study, we investigated the effects of hyperprolactinaemia, induced by transplantation of anterior pituitary glands under the kidney capsule in female rats, on the relationship between serum and pituitary concentrations of the gonadotropins and on the oestrous cycle. 2. Rats with pituitary transplants showed increased serum prolactin concentrations and decreased serum concentrations of gonadotropins and increased pituitary concentrations of gonadotropins. Moreover, these rats showed persistent dioestrous and anovulation from 3 to 6 days after transplantation. 3. A single oral administration of cabergoline (at doses between 0.001 and 0.1 mg/kg) dose-dependently inhibited the elevated serum prolactin concentrations in hyperprolactinaemic rats. At 0.1 mg/kg, cabergoline induced a continuous reduction in serum prolactin concentrations for 5 days after administration. Terguride (0.1 mg/kg) and bromocriptine (10 mg/kg) also reduced serum prolactin concentrations at 1 and 3 days after administration. All three dopamine D2 receptor agonists increased serum gonadotropin concentrations and ovarian weight at 3 days after administration. 4. In rats exhibiting anovulation, a single oral administration of any one of the three dopamine D2 receptor agonists dose-dependently restored ovulation and a normal oestrous cycle appeared. Oral administration of cabergoline (0.03 mg/kg) or terguride (0.1 mg/kg) restored ovarian function and abolished the anovulation following a reduction in serum prolactin concentrations. However, bromocriptine (10 mg/kg) did not completely abolish anovulation. Following administration of terguride (0.3 mg/kg) or bromocriptine (30 mg/kg), only one normal oestrous cycle appeared; however, following cabergoline (0.1 mg/kg), two normal oestrous cycles appeared. 5. These results suggest that cabergoline has a potent and long-lasting action as a dopamine D2 receptor agonist and, thus, should be a useful drug for the treatment of galactorrhoea and hyperprolactinaemic amenorrhoea and/or anovulation in humans.

Impact of environmental temperature on response of neonatal pigs to an endotoxin challenge.

To evaluate the effect of various environmental temperatures (ET) on the ability of neonatal pigs to cope with an endotoxin challenge. 28 crossbred male pigs that were 24 hours old. At 24 hours of age, pigs were placed in environmentally controlled chambers maintained at 18 or 34 C (14 pigs/ET). Rectal temperatures (RT) were recorded at 15-minute intervals for 3 hours following an IP injection of 0.9% NaCl (7 control pigs/ET) or lipopolysaccharide (LPS; 150 microg/kg of body weight; 7 LPS-treated pigs/ET). Tissue specimens and blood samples were collected following the 3-hour challenge period. LPS-treated pigs exposed to 18 C had a period of hypothermia whereas RT for LPS-treated pigs at 34 C did not differ from control pigs. The LPS-treated pigs maintained at 18 C lost the most body weight during the 3-hour period and also had the greatest increase in serum cortisol concentration. Serum prolactin (PRL) concentration was decreased in pigs at 18 C, compared with pigs at 34 C. Challenge with LPS resulted in an increase in serum PRL concentration at 18 C but had no effect on serum PRL at 34 C. Challenge with LPS resulted in an increase in expression of tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 receptor mRNA in the hypothalamus. Exposure to a cold ET can inhibit the ability of neonatal pigs to cope with an exogenous endotoxin challenge. When combined, cold stress and exposure to exogenous endotoxin induces a rapid and potentially dangerous loss of body temperature in neonatal pigs.

Detection of dopaminergic modulators in a tier I screening battery for identifying endocrine-active compounds (EACs)

Apomorphine (APO; D 2 receptor agonist), haloperidol (HAL; D 2 receptor antagonist), and reserpine (RES; a dopamine depletor that acts to lower brain dopamine levels by depleting central nervous system monoamines via disrupting storage vesicle function) have been examined in a Tier I screening battery, which has been designed to detect endocrine-active compounds (EACs). The Tier I battery incorporates two short-term in vivo tests (a 5-day ovariectomized female battery and a 15-day intact male battery using Sprague–Dawley rats) and an in vitro yeast transactivation system (YTS). In addition, two blood collection procedures were evaluated for their utility in detecting HAL-induced increases in serum prolactin (PRL) levels (i.e., the stress associated with each procedure). In the in vivo female battery, both HAL and RES increased serum PRL concentrations as expected, although the increase caused by RES was marginal. Increases in serum PRL levels are enhanced when daily dosages are administered via multiple-daily dosing of the test compound, which results in higher sustained blood levels of the test compounds. APO failed to decrease serum PRL concentrations in the female battery. In the in vivo male battery, HAL increased serum PRL concentrations as expected. However, APO and RES failed to affect serum PRL concentrations. The blood collection comparison experiment demonstrated that possible confounding of the data can occur with serum PRL concentrations when animals are exposed to stress. Basal levels of PRL were approximately fourfold higher in animals that were bled via the tail vein procedure when compared to PRL levels from animals that were bled under CO 2 anesthesia at euthanization. As a result of the higher basal PRL levels, the HAL-induced increase in serum PRL concentrations was completely attenuated in the tail-vein bled animals (1.3-fold). In contrast, HAL produced a fivefold increase in serum PRL in animals where blood was collected under CO 2 anesthesia at euthanization. Hence, collection of blood from animals under CO 2 anesthesia at euthanization is an acceptable approach for detection of compounds that increase PRL. In summary, HAL-like compounds would be identified in the Tier I male and female battery primarily via increased serum PRL concentrations. RES-like compounds would be identified in the Tier I male battery via decreased gonadotropins and steroids and possibly in the Tier I female battery by a minimal increase in serum PRL concentrations. Compounds that produce a marginal increase in serum PRL when administered using single daily dosing can also be confirmed in an in vivo female battery with multiple dosing because this regimen increases the magnitude of the PRL increase. APO, a D 2 receptor agonist, was not detected in the in vivo male or female batteries, but in both instances the top dosage produced minimal decreases in body weight (99 to 96% of control). Hence, the proposed Tier I battery needs to be further evaluated with higher dosages of APO and other D 2 receptor agonists to determine whether it is capable of detecting such agents.

Receptors and neurotransmitters involved in the dual modulation of prolactin release by the serotoninergic system in pregnant and lactating rats.

The receptors and neurotransmitter pathways that may participate in the inhibitory action of 5-hydroxytryptamine (5HT) on prolactin release during late pregnancy and lactation in rats were studied. Administration of the 5HT synthesis inhibitor, p-chlorophenylalanine, to late pregnant rats induced a significant increase in serum prolactin concentrations at 17:00 h on day 19 of pregnancy that was partially blocked by injections of the 5HT precursor, 5-hydroxytryptophan, or the 5HT agonists, 8-hydroxy-2-(di-n-propylamino)-tetralin hydrobromide (S1a), 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (S2) and N-(3-chlorophenyl)imidodicarbonimide diamide HCl (S3), but not by RU 24969 (S1b) or 1-meta-(chlorophenyl)-piperazine-2-HCl (S1a-2c). The 5HT neurotoxins, fenfluramine and p-chloroamphetamine, which selectively destroy fine axon serotoninergic fibres but not coarse ones, prevented the increase in circulating prolactin observed at 18:00 h on pro-oestrus and on day 21 of pregnancy, but did not modify serum prolactin concentrations at 17:00 h on day 19 of pregnancy. Administration of the adrenergic antagonists, metoprolol or prazosin, also prevented the stimulatory effects of p-chlorophenylalanine or ketanserin in pregnant rats on day 19 (17:00 h) or on days 10-12 (16:30 h) in lactating rats separated from their litters. Administration of p-chlorophenylalanine to pregnant rats on day 19 reduced dopamine concentrations in the arcuate nucleus and in the anterior hypothalamus and noradrenaline concentrations in the anterior hypothalamus and the suprachiasmatic nucleus. These results indicate that the inhibitory actions of 5HT on prolactin release in pregnant and lactating rats are mediated by S1a, S2a and S3 receptors and by the coarse axon serotoninergic fibres. In addition, the inhibitory actions of 5HT may modulate the action of a stimulatory adrenergic pathway, as well as the concentrations of noradrenaline and dopamine in different hypothalamic areas, which, in turn, particularly arcuate nucleus dopamine, regulate prolactin release.

Participation of the opioid system in the regulation of prolactin secretion in androgenized rats: effect of ovarian steroids

We examined the role of the opioid system on the regulation of prolactin secretion in neonatally androgenized rats and evaluated the participation of ovarian steroids in this regulation. Androgenized rats exhibited an increase of prolactin secretion with higher serum circulating levels in the afternoon (1800) than in the morning (1000). The administration of the opioid antagonist naloxone (2 mg/kg, 30 min before decapitation) reduced serum prolactin levels in both groups. To identify the opioid receptor subtypes involved in this regulation, opioid agonists were administered i.c.v. 15 min before the decapitation (1000). The μ-opioid receptor agonist DAMGO ([ d-Ala 2, NMe-Phe 4, Gly 5-ol]-enkephalin) caused a significant increase in serum prolactin concentration. The selective κ-opioid receptor agonist U-50, 488H ( trans-(±)-3,4-dichloro- N-[2(1-pyrrolidinyl)-cyclohexyl]-benzene acetamide methane sulfonate salt) induced a small but significant increase in serum prolactin levels but no effect was observed after administration of the δ-opioid agonist DPDPE ([ d-Pen 2, d-Pen 5]-enkephalin). The role of oestradiol and the opioid system in the continuous secretion of prolactin was also study. Chronic gonadectomy (3–4 weeks) reduced serum prolactin concentrations measured at 1000 but the administration of naloxone had no effect. Three days of oestrogen treatment (2 μg/rat in oil) restored serum prolactin levels compared with ovariectomized animals and this effect was abolished by naloxone treatment. Interestingly, acute ovariectomy or administration of tamoxifen to intact androgenized rats did not prevent the continuous secretion of prolactin observed in these animals and naloxone treatment reduced serum prolactin levels in both groups of rats. We also examine the participation of adrenal progesterone and the endogenous opioid peptides on the regulation of prolactin levels in androgenized rats. After adrenalectomy, no changes in serum prolactin levels (1000) were observed compared with the control animal and naloxone treatment significantly reduced circulating prolactin levels. Progesterone treatment to intact androgenized rats significantly increased prolactin levels and the administration of naloxone blocked the stimulatory effect of the steroid. These results suggest that the opioid system play a role in the regulation of prolactin secretion in androgenized rats modulated by the persistence of oestrogen action. Moreover, the presence or absence of progesterone did not modify the regulation of prolactin secretion by the opioids. The μ- and κ-opioid receptor subtypes are the ones involved in the modulation of pituitary prolactin secretion.

Gynecomastia with Risperidone-Fluoxetine Combination

Gynecomastia (breast enlargement) is a side effect of neuroleptic antipsychotic drugs, related to prolactin elevation caused by dopamine D2 receptor blockade (Richelson, 1996). The atypical antipsychotic risperidone is less likely to cause gynecomastia at low doses (Casey, 1996). It can cause a dose-dependent increase in serum prolactin concentration (Peuskens, 1995), by blocking dopamine D2 receptors (Richelson, 1996). I would like to describe a patient who did not have gynecomastia with risperidone at a dose of 3 mg/day, but had it when risperidone, at a dose of 0.5 mg/day, was combined with fluoxetine. A MEDLINE search failed to find any reports about such an interaction.

Relationship between induction of mammary tumors and change of testicular functions in male rats following gamma-ray irradiation and/or diethylstilbestrol.

Male Wistar-MS (W/MS), Fisher-344 (F-344) and Sprague-Dawley (SD) rats were divided into four groups including a control group implanted with a cholesterol pellet. Rats in the three experimental groups were treated with gamma-ray irradiation (260 cGyt) alone, diethylstilbestrol (DES) pellet implantation alone or both irradiation and DES, and all rats were observed for detection of mammary tumors for 1 year. Morphologically, well-developed mammary glands were observed in the SD rats at ages corresponding to the time of irradiation. But, the mammary glands in the W/MS and F-344 rats showed a lower degree of differentiation than those in the SD rats. No mammary tumor developed spontaneously in the W/MS and F-344 strains of rats during the experimental period. The rats administered both DES and irradiation showed significantly increased incidence of mammary tumors compared with the control, the incidence being 80.9% in the SD rats, 35.0% in the W/MS rats, and 9.4% in the F-344 rats, respectively. The incidence of tumor in the SD rats treated with irradiation alone and with DES alone was 9.5% and 14.3%, respectively, but no tumor development was observed in the F-344 rats treated with either irradiation alone or DES alone or in the W/MS rats treated with DES alone. The magnitude of the decrease of testicular weight in the SD rats implanted with DES after irradiation (to 70% of the control weight) was slightly less marked than that in either the W/MS (35%) or F-344 (16%) rats. The testicular atrophy showed a correlation with the accessory sex organ weight at the end of the experiment, serum testosterone concentration, and incidence of mammary tumors. Following administration of DES pellets after the irradiation, the activity of delta 5-3 beta- and of 17 beta-hydroxysteroid dehydrogenase in the testes showed the order F-344 < W/MS = SD and F-344 = W/MS < SD, respectively. Compared with the control, the irradiated F-344 rats implanted with DES pellets showed hypertrophied pituitary glands (10.7-fold, P < 0.01) as well as increased serum prolactin concentration (21.4-fold, P < 0.01). Of the three strains treated with both irradiation and DES, the F-344 rats showed the highest concentration of serum prolactin but the lowest incidence of mammary tumors. Our results suggest that W/MS, F-344 and SD male rats have differing susceptibilities for the induction of mammary tumor following irradiation. We discuss the relationship between testicular and pituitary functions and male mammary tumorigenesis.

Antibody binding of circulating ergot alkaloids in cattle grazing tall fescue

Summary Direct evidence linking alkaloids found in endophyte-infected tall fescue forage with the livestock disorder known as fescue toxicosis is lacking. Physiologic effects of fescue toxicosis include reduced serum prolactin concentration in cattle. A monoclonal antibody specific to the lysergic moiety of ergot alkaloids was developed in mice after creating an immunogen by linking lysergol to human serum albumin. The antibody was specific to the lysergic moiety and, therefore, it cross-reacted with ergot alkaloids, lysergic acid, and lysergol. The antibody did not cross-react with alkaloid derivatives that had bromated or hydrogenated lysergic ring moieties. Fescue toxicosis conditions were elicited in yearling Angus steers by permitting them to graze endophyte-infected tall fescue containing &gt; 650 μg/kg of ergovaline for 60 days. Passive immunization of steers by infusion of the monoclonal antibody increased serum prolactin concentration by 7 ng/ml, beginning immediately after infusion. Control steers did not respond to treatment with bovine serum albumin. Active immunization of yearling Angus heifers with immunogens containing lysergol or ergonovine linked to human serum albumin resulted in an antibody response.

Stimulation of prolactin secretion by melatonin is not mediated by opioids.

To clarify the role the opioid system plays in mediating the stimulation of prolactin release by melatonin, we performed two separate studies between the 6th and 8th days of the follicular phase in normal young women. In the first study, serum prolactin concentrations were determined every 20 min over a 4-hour period following oral administration of melatonin (1 mg given at 13.00 h) in the presence of continuous intravenous infusion of saline or naloxone (1.6 mg/h), an opiate antagonist. In the second study, plasma beta-endorphin concentrations were measured over a 3-hour period following oral melatonin administration (1 mg given at 13.00 h). Oral melatonin administration alone induced a significant increase in serum prolactin concentration, which was maximal 3 h after melatonin administration. Prolactin release following melatonin administration was not affected by continuous intravenous infusion of naloxone. No significant change in plasma beta-endorphin concentrations was observed following melatonin administration. These findings strongly suggest that the stimulation of prolactin release by melatonin is not mediated by opioids.