Basal Prolactin Concentrations Research Articles

Hepatitis-C Patients Have Reduced Growth Hormone (GH) Secretion Which Improves During Long-Term Therapy With Pegylated Interferon-α

In vitro and in vivo data indicate multiple, but contradictory effects of interferon on pituitary hormone secretion. We therefore investigated prospectively basal and stimulated pituitary hormone secretion in 21 patients with chronic hepatitis C virus (HCV) infection before and during antiviral therapy. Twenty-one patients received pegylated interferon-alpha plus either ribavirin or levovirin. Baseline and stimulated growth hormone (GH), cortisol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (PRL), and thyroid-stimulating hormone (TSH) responses were measured using standard pituitary function tests, before therapy in all and during therapy in 17 out of the 21 patients. Before therapy 17 patients (81%) had severe GH insufficiency and 9 of these had low insulin-like growth factor-1 (IGF-1) concentrations. Basal and stimulated GH concentrations increased significantly during therapy, reducing the number of patients with severe GH insufficiency to four, but IGF-1 remained low. Basal PRL and TSH concentrations were normal before and during therapy, while thyroid-releasing hormone (TRH)-stimulated concentrations increased significantly during therapy. The adrenocorticotropic hormone (ACTH)/cortisol axis, basal and stimulated gonadotropin, and testosterone concentrations were normal throughout. Neither the HCV RNA level nor transaminases correlated with hormone concentrations before or during therapy. GH insufficiency is common in patients with chronic HCV infection. While GH secretion improves during antiviral therapy, IGF-1 remains low, indicating persistent GH resistance of hepatocytes. Whether improvement in GH secretion during treatment is due to a direct drug effect or related to the suppression of viral load could not be differentiated, as most patients demonstrated a positive virologic response.

Prolactin reference range and pulsatility in male dogs

Little is known about serum prolactin (PRL) concentrations and secretion patterns in male dogs. Blood samples ( n = 65) were collected from crossbred dogs and from Beagles and German Shepherd dogs to describe the PRL reference range, and from five male Beagles at 15-min intervals for 6 h ( n = 24 samples/dog) to describe the ultradian rhythm of this hormone. Serum PRL was measured by a homologous endpoint enzyme immunometric assay. The reference range was established from nondetectable to 6.0 ng/mL. There was an effect of breed; serum PRL concentrations in Beagles were higher ( P < 0.05) than in crossbreeds and German Shepherds. However, there was no significant correlation between PRL concentration and age of the dog. During the ultradian study, PRL was characterized by a fluctuating baseline with occasional distinct elevations, indicating a pulsatile secretion. The mean basal PRL concentration was 1.4 ± 0.6 ng/mL and the mean AUC was 9.9 ± 2.7 ng/mL/6 h. Prolactin pulse frequency ranged from one to two peaks/6 h, pulse duration between 15 and 75 min, and amplitude from 1.7 to 2.4 ng/mL. In conclusion, this reference range, pulsatility and breed differences should be taken into account when interpreting serum PRL concentrations, for clinical or research purposes.

Ovariectomy during the luteal phase influences secretion of prolactin, growth hormone, and insulin-like growth factor-I in the bitch

A decline in circulating progesterone concentration plays an important role in the ethiopathogenesis of pseudopregnancy in the bitch. Because growth hormone (GH) and prolactin (PRL) are essential for normal mammogenesis and the secretion of these hormones is influenced by changes in the circulating progesterone concentration, the purpose of this study was to investigate the effects of mid-luteal phase ovariectomy on the 6-h pulsatile plasma profiles of GH and PRL and the basal plasma concentrations of GH, PRL, and insulin-like growth factor-I (IGF-I) in six beagle bitches. Ovariectomy was followed by only mild or covert signs of pseudopregnancy. The sharp decrease of the plasma progesterone concentration was accompanied by decreased basal plasma concentrations of GH and IGF-I and a rise in basal plasma PRL concentration. GH and PRL were secreted in a pulsatile fashion both prior to and after ovariectomy. The mean basal plasma GH concentration was significantly higher before ovariectomy than on days 1 and 7 after ovariectomy. The mean area under the curve above the zero level (AUC 0) for GH was significantly higher before than at 7 days after ovariectomy. The mean area under the curve above basal level (AUC b) and the frequency of GH pulses at 7 days after ovariectomy were significantly higher than before and 1 day after ovariectomy. Both the mean basal plasma PRL concentration and the mean AUC 0 for PRL increased after ovariectomy. In conclusion, ovariectomy of bitches in the mid-luteal phase stops progesterone-induced GH release from the mammary gland, as evidenced by the lowering of basal plasma GH levels, the recurrence of GH pulsatility, and the lowering of circulating IGF-I levels. The sudden lowering of plasma progesterone concentration is probably a primary cause of a prolonged increase in PRL secretion. These observations underscore the importance of similar, albeit less abrupt, hormonal changes in the cyclical physiological alterations in the mammary gland and in the development of pseudopregnancy.

Adenohypophyseal function in bitches treated with medroxyprogesterone acetate

The aim of this study was to investigate the effects of treatment with medroxyprogesterone acetate (MPA) on canine adenohypophyseal function. Five Beagle bitches were treated with MPA (10 mg/kg, every 4 weeks) and their adenohypophyseal function was assessed in a combined adenohypophyseal function test. Four hypophysiotropic hormones (CRH, GHRH, GnRH, and TRH) were administered before and 2, 5, 8, and 11 months after the start of MPA treatment, and blood samples for determination of the plasma concentrations of ACTH, cortisol, GH, IGF-1, LH, FSH, prolactin, α-MSH, and TSH were collected at −15, 0, 5, 10, 20, 30, and 45 min after suprapituitary stimulation. MPA successfully prevented the occurrence of estrus, ovulation, and a subsequent luteal phase. MPA treatment did not affect basal and GnRH-induced plasma LH concentrations. The basal plasma FSH concentration was significantly higher at 2 months after the start of MPA treatment than before or at 5, 8, and 11 months after the start of treatment. The maximal FSH increment and the AUC for FSH after suprapituitary stimulation were significantly higher before treatment than at 5, 8, and 11 months of MPA treatment. Differences in mean basal plasma GH concentrations before and during treatment were not significant, but MPA treatment resulted in significantly elevated basal plasma IGF-1 concentrations at 8 and 11 months. MPA treatment did not affect basal and stimulated plasma ACTH concentrations, with the exception of a decreased AUC for ACTH at 11 months. In contrast, the maximal cortisol increment and the AUC for cortisol after suprapituitary stimulation were significantly lower during MPA treatment than prior to treatment. MPA treatment did not affect basal plasma concentrations of prolactin, TSH, and α-MSH, with the exception of slightly increased basal plasma TSH concentrations at 8 months of treatment. MPA treatment did not affect TRH-induced plasma concentrations of prolactin and TSH. In conclusion, the effects of chronic MPA treatment on adenohypophyseal function included increased FSH secretion, unaffected LH secretion, activation of the mammary GH-induced IGF-I secretion, slightly activated TSH secretion, suppression of the hypothalamic–pituitary–adrenocortical axis, and unaffected secretion of prolactin and α-MSH.

Bromocriptine treatment for cocaine addiction: Association with plasma prolactin levels

Bromocriptine is a dopamine receptor agonist used with mixed success in the treatment of cocaine addiction. Variations in dopamine receptor sensitivity may help account for these differences. We evaluated this question in a 24-week outpatient controlled clinical trial in 70 cocaine-abusing (DSM-III) men (86% African–American, mean age 34 years, mean 39 months of regular cocaine use [predominantly smoked]). Subjects received 4 weeks of inpatient treatment. During the last 2 weeks they were inducted onto bromocriptine (maximum dose 2.5 mg po tid) ( n = 35) or placebo ( n = 35). Plasma prolactin concentrations were assayed before and after the first bromocriptine dose (1.25 mg po) as a measure of dopamine receptor sensitivity. After discharge, subjects continued on medication with weekly group counseling. Bromocriptine significantly suppressed prolactin concentrations (4.4 ng/ml decrease), while placebo did not (0.1 ng/ml decrease). Both groups decreased their cocaine use, with no significant group differences in retention in treatment or proportion of cocaine-positive urine samples. There was no significant association between basal plasma prolactin concentrations or prolactin response to first bromocriptine dose and either outcome measure. These data do not support the efficacy of bromocriptine treatment nor a role for prolactin concentration in predicting treatment response.

The Roles of Dopamine and the Neurointermediate Lobe of the Pituitary in the Regulation of Prolactin Secretion During Late Pregnancy in Rats

The major hypothalamic control over prolactin secretion from the anterior pituitary gland is inhibitory by means of dopamine released from tuberoinfundibular dopamine (TIDA) neurones. We have previously shown a dissociation between activity of TIDA neurones and prolactin secretion during late pregnancy, suggesting involvement of additional regulatory factors. The aim of the present study was to investigate the role of dopamine and the neurointermediate lobe (NIL) of the pituitary in the regulation of prolactin secretion during late pregnancy. To determine whether dopamine maintains inhibition of prolactin during late pregnancy, the D(2) receptor antagonist domperidone was administered at 12.00 h on days 18 and 21 of pregnancy. These times are characterized by high and low TIDA neuronal activity, respectively, and low prolactin secretion. Domperidone produced an immediate increase in plasma prolactin compared to vehicle-treated controls on both days 18 and 21. Thus, dopaminergic inhibition of prolactin secretion is maintained despite reduced TIDA neuronal activity at the end of pregnancy. The contribution of NIL-derived dopamine in regulating prolactin secretion was then examined by investigating the effect of surgical removal of the NIL. NIL removal produced significantly increased basal prolactin concentrations, indicating that dopamine from the NIL contributes to the suppression of prolactin before the antepartum prolactin surge. Furthermore, NIL removal also completely prevented the antepartum prolactin surge compared to sham-operated controls, which is consistent with the hypothesis that the NIL supplies a prolactin-releasing factor to the anterior pituitary to induce the antepartum prolactin surge.

Relationship of serum prolactin with severity of drug use and treatment outcome in cocaine dependence

Alteration in serum prolactin (PRL) levels may reflect changes in central dopamine activity, which modulates the behavioral effects of cocaine. Therefore, serum PRL may have a potential role as a biological marker of drug severity and treatment outcome in cocaine dependence. We investigated whether serum PRL levels differed between cocaine-dependent (CD) subjects and controls, and whether PRL levels were associated with severity of drug use and treatment outcome in CD subjects. Basal PRL concentrations were assayed in 141 African-American (AA) CD patients attending an outpatient treatment program and 60 AA controls. Severity of drug use was assessed using the Addiction Severity Index (ASI). Measures of abstinence and retention during 12 weeks of treatment and at 6-month follow-up were employed as outcome variables. The basal PRL (ng/ml) in CD patients (9.28+/-4.13) was significantly higher than controls (7.33+/-2.94) (t=3.77, P<0.01). At baseline, PRL was positively correlated with ASI-drug (r=0.38, P<0.01), ASI-alcohol (r=0.19, P<0.05), and ASI-psychological (r=0.25, P<0.01) composite scores, and with the quantity of cocaine use (r=0.18, P<0.05). However, PRL levels were not significantly associated with number of negative urine screens, days in treatment, number of sessions attended, dropout rate or changes in ASI scores during treatment and at follow-up. Also, basal PRL did not significantly contribute toward the variance in predicting any of the outcome measures. Although cocaine use seems to influence PRL levels, it does not appear that PRL is a predictor of treatment outcome in cocaine dependence.

Do basal oestradiol and oestradiol:androgens and oestradiol: FSH ratios reflect pregnancy potential of women receiving intrauterine insemination during natural cycles?

The aim of this retrospective study was to evaluate whether basal hormone profiles could be related to the ability to achieve pregnancy in women receiving intrauterine insemination (IUI) treatment during their natural menstrual cycle. Serum hormone profiles on cycle day 3 of naturally menstruating women were assessed in a total of 163 treatment cycles (29 conceptional and 53 non-conceptional cycles of 27 women who became pregnant and 81 non-conceptional cycles of 33 women who did not become pregnant). Basal concentrations of LH, FSH and prolactin were similar between conceptional and non-conceptional cycles. In contrast, concentrations of oestradiol in conceptional cycles (38 · 26 pg/ml: mean · SD) were significantly higher than those in non-conceptional cycles (23 · 18 pg/ml) ( P = 0.0003). Concentrations of androstenedione and testosterone were lower but not significantly so in conceptional cycles as compared with non-conceptional cycles. The ratios of oestradiol/androstenedione, oestradiol/testosterone and oestradiol/FSH were significantly higher in conceptional as compared with non-conceptional cycles (29, 2.3, 6.2 versus 17, 1.2, 3.6 respectively) (all P < 0.006). Thus, increased concentrations of oestradiol and increased oestradiol/androgens and oestradiol/FSH ratios already on day 3 of the natural menstrual cycle correlate with the likelihood of achieving conception during the following IUI treatment. Therefore, measurement of basal hormones, including androstenedione and testosterone, may be useful to assess the health status of the coming dominant follicle.

Somatotropic, lactotropic and adrenocortical responses to insulin-induced hypoglycemia in patients with rheumatoid arthritis.

Neuroendocrine mechanisms have been suggested to play an important role in the onset and progression of rheumatoid arthritis (RA). The aim of this study was to evaluate hypothalamic-pituitary functions in RA patients by measurement of hormone responses to insulin-induced hypoglycemia. Insulin-hypoglycemia (Actrapid HM 0.1 IU/kg, i.v. as a bolus) was induced in 17 male patients and in 11 age-, gender-, and weight-matched healthy subjects. Concentrations of growth hormone (GH), prolactin (PRL) and cortisol were analyzed in plasma. PRL release after thyreoliberin stimulation (TRH, 200 g, i.v.) was determined in 21 patients with active forms of RA and in 12 control subjects to evaluate pituitary lactotropic response. In RA patients, basal concentrations of glucose, GH, PRL, and cortisol were in the normal range and they were comparable to those in the control group. Stress of hypoglycemia induced significant elevation of GH, PRL, and cortisol concentrations in all groups. Cortisol responses to hypoglycemia were comparable in patients and in control subjects. GH release during hypoglycemia was increased (p < 0.05) and PRL response was attenuated (p < 0.05) in RA patients versus control subjects. After TRH administration, PRL response was the same in patients as in healthy subjects. In conclusion, the present study revealed an altered hypothalamic-pituitary function in patients with RA, namely, an enhanced somatotropic and reduced lactotropic activation in response to insulin-induced hypoglycemia. Basal hormone levels and cortisol release during hypoglycemia were similar to those in healthy subjects.

Effects of risperidone on gonadal axis hormones in schizophrenia.

To investigate the effects of risperidone on the hypothalamo-pituitary-gonadal (HPG) axis of chronic schizophrenic male inpatients medicated regularly. Subjects included six inpatients who were diagnosed according to the Diagnostic and Statistical Manual, Fourth Edition, criteria for schizophrenia, and were termed treatment-refractory. Each patient gave informed consent for the research involved in this study. The neuroendocrine studies were done before and during risperidone administration. Patients took a mean dose of risperidone 9.5 mg/d for a mean period of 64.2 days. Psychotic symptoms were assessed using the Brief Psychiatric Rating Scale (BPRS). Prolactin (PRL) increased significantly during risperidone administration. However, luteinizing hormone, follicle-stimulating hormone, and testosterone did not show significant difference between blood concentrations before and during risperidone administration. Scores of the BPRS total, thought disturbance factor, and tension decreased significantly during risperidone administration. Throughout the study, none of the patients experienced clinically significant problems associated with elevated PRL concentrations including gynecomastia and/or sexual dysfunction. Addition of risperidone produced significant improvement of psychotic symptoms in treatment-resistant schizophrenic patients, and an increase in basal blood PRL concentrations, but not in basal blood HPG axis hormone concentrations. This preliminary result warrants further double-blind evaluation with a larger sample.

Assessment of pituitary gonadotropin release to gonadotropin releasing hormone/thyroid-stimulating hormone stimulation in women with systemic sclerosis.

To evaluate basal and dynamic levels of pituitary gonadotropin release in female systemic sclerosis (SSc) patients of childbearing age and in post-menopausal SSc patients. We performed stimulation tests for gonadotropin-releasing hormone (GnRH) and thyroid-stimulating hormone (TRH) during the early follicular phase in 12 women of childbearing age [mean age (S.E.M.) 34.8 (2.4) yr] with SSc to determine serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and prolactin. Blood samples were also obtained from six post-menopausal women with SSc [mean age 46.8 (2.4) yr], after TRH stimulation; only serum prolactin concentration was determined, because elevated basal concentrations of FSH and LH were expected. Hormone concentrations were estimated by radioimmunoassay. Comparisons were made with healthy control women matched for age and reproductive status. In SSc patients of childbearing age, basal FSH, LH and oestradiol (E(2)) levels were not significantly different from those in controls, whereas basal prolactin concentration was significantly higher than in controls (P=0.0001). After the stimulation test, the peak concentrations of FSH (P=0.0001) and prolactin (P<0.0001) were significantly higher than in controls. The net integrated response curves [net area under the curve (AUC)] for FSH and LH did not differ significantly between SSc patients and controls. On the contrary, the net AUC for prolactin in response to TRH stimulation was significantly higher than in controls (P=0.001). In post-menopausal patients, basal E(2), FSH, LH and prolactin levels were not significantly different between women with SSc and controls. However, after TRH stimulation, peak levels and net AUC for prolactin were not significantly higher in patients than those in controls. No significant correlations were found between basal and stimulated FSH, LH and prolactin levels and the severity of involvement of various organ systems. Multiple regression analysis showed that basal and stimulated prolactin concentrations were associated with skin sclerosis and peripheral vascular and lung involvement. Our results suggest that subclinical primary hypogonadism can occur in SSc patients. They also confirm an alteration in the mechanism for prolactin secretion and release, which may not only contribute to further disturbance of the reproductive axis but may also have an influence on the disease.

Endocrine profiles during doe-litter separation and the subsequent pregnancy in rabbits

This study was carried out to determine the effects of a transient doe-litter separation on plasma prolactin, LH, FSH, estradiol-17beta and progesterone concentrations before artificial insemination and during the subsequent pregnancy. Control does (n=12) had free access to nursing, whereas separated does (n=12) were kept away from their litters for 48 hours before artificial insemination. Both groups were inseminated on day 11 after parturition. Teat stimulation by suckling caused a high increase in prolactin concentrations in separated does (p < 0.0001). Basal prolactin concentrations were observed in both groups on days 8 and 18 of pregnancy. No effect of the treatment was detected on LH and FSH concentrations during the sampling period. A rise of estradiol-17beta concentrations was observed 48 hours after doe-litter separation, compared to control does and to previous values (p < 0.003). Both groups showed low progesterone concentrations before artificial insemination. Pregnant rabbits in both groups showed increased progesterone concentrations on days 8 and 18 of pregnancy. Lower estradiol-17beta concentrations were observed in control does on day 18 of pregnancy compared with separated rabbits (p < 0.003). The results suggest that a transient separation of nursing does from their litters before artificial insemination may promote high follicular steroidogenesis activity leading to increased estradiol-17beta concentrations. This hormonal change could be a result of several stimulatory actions probably triggered by the absence of suckling episodes and may affect the luteotrophic function during the subsequent pregnancy.

Abstracts of the Internistendagen 2001

Background: In patients with hyperprolactinemia, the thyrotropin-releasing hormone (TRH) stimulation test is widely applied to distinguish prolactinoma from other causes of hyperprolactinemia. In the present study, we established reference values for the plasma concentration of prolactin (PRL) and its response to TRH.Methods: Basal PRL and the PRL response to 400 μg TRH iv was determined in 50 subjects recruited from the general population, equally distributed according to sex and age between 20 and 69 years. PRL was determined by a fluoroimmunometric assay. Reference values are given as the observed range.Results: Plasma concentrations of PRL were 4.0–25 μg/l (median: 10.0 μg/l) in women and 0.5–19.0 μg/l (median: 8.5 μg/l) in men (p=0.11). The peak PRL concentration after stimulation with TRH was slightly higher in women (median: 51 μg/l) than in men (median: 41 μg/l; p=0.04) and was reached at t=20 min in all subjects. The relative increase in plasma PRL (median: 440%) did not show a statistically significant effect of age or sex. In 12 subjects (24%), the relative increase in plasma PRL was lower than 250%, which has traditionally been considered the minimum cutoff for a normal response. There were no effects of smoking and alcohol, but regular ingestion of liquorice was associated with lower basal (p=0.03) and lower stimulated (p=0.05) plasma concentrations of PRL.Conclusions: The present study provides reference values for basal and TRH-stimulated plasma concentrations of PRL.

Endocrine and Metabolic Effects of Insulin Sensitizers in the Treatment of Patients with Polycystic Ovary Syndrome and Hyperinsulinaemia

We evaluated 16 women with polycystic ovary syndrome (PCOS) and 67 controls, aged 18–34 years. All subjects had an oral glucose tolerance test (OGTT), showing a normal response. They were subdivided into 2 groups (normoinsulinaemic, hyperinsulinaemic) undergoing 7 days of octreotide treatment. This caused modifications in body mass index, waist-hip ratio and blood pressure. No modifications were observed in basal luteinizing hormone (LH), follicle-stimulating hormone, androgens, 17α-hydroxyprogesterone, oestradiol, sex-hormone-binding globulin (SHBG), prolactin and cortisol serum concentrations in normoinsulinaemic patients. A significant decrease in the concentration of LH, androgens, and a significant increase in SHBG were observed in the hyperinsulinaemic patients. In hyperinsulinaemic patients, the treatment restored a regular insulinaemic response to an OGTT. No modifications of glycaemic response were detected in normoinsulinaemic ones. In hyperinsulinaemic patients, a decompensation of the glycaemic response was observed. Several agents (insulin sensitizers) decrease insulin secretion and androgen concentration. They could be considered an approachable long-term therapy for hyperinsulinaemic hyperandrogenic patients. In the next few years the pharmacotherapy for PCOS could be greatly expanded, allowing some patients, such as hyperinsulinaemic ones, to be treated with insulin sensitizers.

Combined pituitary hormone deficiency in German shepherd dogs with dwarfism

In German shepherd dogs pituitary dwarfism is known as an autosomal recessive inherited abnormality. To investigate whether the function of cells other than the somatotropes may also be impaired in this disease, the secretory capacity of the pituitary anterior lobe (AL) cells was studied by a combined pituitary AL stimulation test with four releasing hormones (4RH test) in four male and four female German shepherd dwarfs. In addition, the morphology of the pituitary was investigated by computed tomography. The physical features of the eight German shepherd dwarfs were primarily characterized by growth retardation and stagnant development of the hair coat. The results of the 4RH test confirmed the presence of hyposomatotropism. The basal plasma TSH and prolactin concentrations were also low and did not change upon stimulation. Basal plasma concentrations of LH were relatively low and responded only slightly to suprapituitary stimulation. With respect to the plasma FSH levels there was a clear gender difference. In the males plasma FSH concentrations remained below the detection limit throughout the 4RH test, whereas in the females the basal plasma FSH levels were slightly lower and there was only a small increase following suprapituitary stimulation, compared with the values in age-matched controls. In contrast, basal and stimulated plasma ACTH concentrations did not differ between the dwarfs and the controls. Computed tomography of the pituitary fossa revealed a normal sized pituitary with cysts in five dogs, an enlarged pituitary with cysts in two dogs, and a small pituitary gland without cysts in the remaining dog. The results of this study demonstrate that German shepherd dwarfs have a combined deficiency of GH, TSH, and prolactin together with impaired release of gonadotropins, whereas ACTH secretion is preserved. The combined pituitary hormone deficiency is associated with cyst formation and pituitary hypoplasia.

Neuroendocrine Manifestations in Sjögren's Syndrome: Relation to the Neurobiology of Stress

Evidence suggests that autoimmune rheumatic diseases are associated with neuroendocrine dysfunction. Sjögren's syndrome (SS) is proposed as an ideal model to study perturbations in the neuroimmune axis, since patients tend to be medication free and studies are not confounded by the effects of chronic immunosuppressive therapy. The functional integrity of the adrenal, gonadal, and thyroid axes was assessed in SS. Pituitary function of the HPA axis was evaluated directly by determining the ACTH released during oCRH stimulation, while adrenal function was assessed indirectly by endogenous ACTH released during oCRH stimulation. Low basal activity of the HPA axis was associated with pituitary hyporesponsiveness to exogenous CRH, as well as hyporesponsiveness of the adrenal glands to endogenous ACTH. These findings are compatible with a central deficiency of the adrenal axis. An overall attenuated and delayed LH and FSH response to LHRH stimulation was also indicative of central dysfunction of the gonadal axis in SS. SS patients demonstrated elevated basal TSH levels and evidence of mild hypothyroidism. Basal prolactin concentrations were also elevated in SS, and both TSH and PRL showed relatively increased responses to TRH stimulation. The data suggest a central deficiency in all three neuroendocrine axes: adrenal, gonadal, and thyroid. It is not clear if any one system plays a primary role in the expression of the disease. Rather, it is likely that the net effect involves the synergistic and antagonistic effects of multiple hormones. Taken together, adrenal and gondadal steroid hormone deficiency, plus elevated PRL levels, probably greatly affect immune function in SS patients.

Establishment of reference values for endocrine tests II: Hyperprolactinemia

Background: In patients with hyperprolactinemia, the thyrotropin-releasing hormone (TRH) stimulation test is widely applied to distinguish prolactinoma from other causes of hyperprolactinemia. In the present study, we established reference values for the plasma concentration of prolactin (PRL) and its response to TRH.Methods: Basal PRL and the PRL response to 400 μg TRH iv was determined in 50 subjects recruited from the general population, equally distributed according to sex and age between 20 and 69 years. PRL was determined by a fluoroimmunometric assay. Reference values are given as the observed range.Results: Plasma concentrations of PRL were 4.0–25 μg/l (median: 10.0 μg/l) in women and 0.5–19.0 μg/l (median: 8.5 μg/l) in men (p=0.11). The peak PRL concentration after stimulation with TRH was slightly higher in women (median: 51 μg/l) than in men (median: 41 μg/l; p=0.04) and was reached at t=20 min in all subjects. The relative increase in plasma PRL (median: 440%) did not show a statistically significant effect of age or sex. In 12 subjects (24%), the relative increase in plasma PRL was lower than 250%, which has traditionally been considered the minimum cutoff for a normal response. There were no effects of smoking and alcohol, but regular ingestion of liquorice was associated with lower basal (p=0.03) and lower stimulated (p=0.05) plasma concentrations of PRL.Conclusions: The present study provides reference values for basal and TRH-stimulated plasma concentrations of PRL.

The hypothalamic-pituitary response in SLE. Regulation of prolactin, growth hormone and cortisol release.

It has been suggested that neuroendocrine regulation plays an important role in the pathogenesis and activation of autoimmune diseases. The aim of this investigation was to clarify the hypothalamic-pituitary response to a well-defined stimulus under standardised conditions in patients with SLE. Plasma concentrations of prolactin (PRL), growth hormone (GH) and cortisol were determined in venous blood drawn through an indwelling cannula during insulin-induced hypoglycaemia (0.1 U/kg b.w., i.v.) in ten patients and in 12 age-, gender- and weight-matched healthy subjects. Basal PRL concentrations were higher in patients vs healthy controls (12 vs 6 ng/ml, P < 0.01), though still within the physiological range. Insulin-induced plasma PRL and GH were significantly increased both in patients and healthy subjects; however, the increments or areas under the curves were not different in the two groups. Plasma cortisol response showed moderate attenuation in patients. Sensitivity of pituitary lactotrothrops to thyrotropin-releasing hormone (TRH) administration (200 microg, i.v.) was the same in patients and control subjects. In SLE patients with low activity of the disease the sensitivity of pituitary PRL release to TRH administration remained unchanged. The hypothalamic response to stress stimulus (hypoglycaemia) was comparable in patients and healthy subjects.

Genetic and environmental influences on prolactin secretion during wake and during sleep.

To delineate the contributions of genetic and environmental factors in the regulation of human prolactin (PRL) secretion, the 24-h profile of plasma PRL was obtained at 15-min intervals in 10 pairs of monozygotic and 10 pairs of dizygotic twins. Sleep was monitored polygraphically. PRL secretory rates were derived from plasma concentrations by deconvolution. Diurnal (24-h) variations were quantified by a regression curve to define nadir, acrophase, and amplitude. Pulses of PRL secretion were identified using a computerized algorithm. A procedure specifically developed for twin studies was used to partition the variance into genetic and environmental contributions. Significant genetic effects were identified for daytime PRL concentrations, rhythm amplitude, and overall wave-shape of the daily PRL profile. In contrast, environmental effects were dominant for mean concentrations during sleep, total secretory output during sleep, overall 24-h concentrations, and total 24-h secretion. However, when interindividual variations in sleep fragmentation were taken into account, the estimates of genetic variance for PRL concentrations and secretion during sleep approached statistical significance. Significant genetic influences were identified for slow-wave sleep (SWS). Because SWS is associated with increased nocturnal PRL secretion, it is possible that genetic effects on PRL secretion during sleep reflect genetic influences on SWS. In conclusion, genetic factors determine partially both the basal daytime concentrations of PRL and the temporal organization of PRL secretion over the 24-h cycle in normal young men.

Effects of N-methyl-D-aspartic acid and kainic acid on prolactin secretion in hyper- and hypoprolactinaemic conditions.

The stimulatory and inhibitory effects of N-methyl-D-aspartic acid (NMDA) and kainic acid on prolactin (PRL) secretion have been correlated with the serum prolactin concentrations before drug administration. In the present experiments, we analysed the role of NMDA and kainic acid in PRL secretion in females with different serum concentrations of PRL. Hypoprolactinaemic females were obtained by ovariectomy or after administration of diethyldithiocarbamate (an inhibitor of dopamine-beta-hydroxylase). Chronic hyperprolactinaemia was induced by neonatal administration of testosterone or oestradiol and acute hyperprolactinaemia was induced either by administration of alpha-methyl-p-tyrosine (an inhibitor of tyrosine hydroxylase) or by ether exposure. To analyse the role of dopamine in the effects of NMDA, we measured pituitary concentrations of dopamine after NMDA treatment and the effects of pretreatment with domperidone. (1) NMDA, but not kainic acid, stimulated PRL release in cyclic females. This effect was independent of serum PRL concentrations and was not accompanied by a decrease in pituitary concentrations of dopamine. (2) NMDA did not change PRL secretion in neonatally androgenized females, whereas NMDA and kainic acid inhibited PRL release in neonatally oestrogenized females. The inhibitory effects of NMDA and kainic acid were blocked by domperidone. (3) Kainic acid inhibited PRL secretion in prepubertal hyper- and hypoprolactinaemic rats. (4) Hyperprolactinaemia induced by ether stress was counteracted by administration of NMDA and kainic acid. (a) NMDA has a dual effect on prolactin secretion that is independent of prior prolactin concentrations and of dopamine activity, but kainic acid is only inhibitory. (b) The stimulatory or inhibitory effects of NMDA and kainic acid on PRL secretion were not strictly related to basal PRL concentrations and necessarily involved a change in the secretion of prolactin releasing factors, as no correlations were observed between changes in pituitary concentrations of dopamine and serum PRL concentrations. (c) Females rendered hyperprolactinaemic by neonatal administration of testosterone or oestradiol responded differently after NMDA administration. (d) NMDA and kainic acid blocked the mechanisms involved in stress-induced PRL secretion.