Basal Prolactin Concentrations Research Articles

Population Pharmacokinetic Analysis of Follicle-Stimulating Hormone During Ovarian Stimulation: Relation with Weight, Prolactin and Gene Polymorphism in THADA and ADIPOQ.

Personalisation strategies of ovarian stimulation for in vitro fertilisation (IVF)/ intracytoplasmic sperm injection (ICSI) treatments using exogenous follicle-stimulating hormone (FSH) have been extensively studied over the past 20 years. This research aimed to develop a FSH population pharmacokinetic (PPK) model taking into account the contribution of gene polymorphisms in Chinese reproductive-age women. Data from 173 patients undergoing GnRH agonist down-regulation long protocols of IVF/ICSI treatment were collected. PPK analysis was subsequently conducted using the nonlinear mixed-effect model (NONMEM) software. Several covariates, including 18 single nucleotide polymorphisms, demographic factors and biological characteristics, were evaluated. The final PPK model was extensively validated using bootstrapping and normalised prediction error distribution, as well as external validation on an independent group of 35 patients. FSH PPK was accurately described by a one-compartment model with first-order absorption. The typical population value of apparent clearance was estimated to be 0.81 L/h [relative standard errors (RSE) 5.3%] with an inter-individual variability (IIV) of 16.0%. The typical apparent distribution volume was 8.36 L (RSE 9.7%, 59.7% IIV), and the absorption rate constant was estimated to be 0.0444 h-1 (RSE 9.1%). Body weight, basal prolactin concentration and the gene ADIPOQ (rs1501299) showed a significant covariate effect on the FSH clearance rate and exposure concentration. Genotypes of THADA (rs12478601) significantly influenced the distribution volume. Simulation results indicated that patients with the TT genotype of THADA (rs12478601) required a longer time to reach steady state and had less fluctuation in FSH levels. Model evaluations showed that the final model accurately and precisely described the observed data and demonstrated effective prediction performance. PPK models of FSH have been developed, which could potentially be used for FSH dosage individualisation in the clinical setting. This study has been registered with the Chinese Clinical Trials Registry (ChiCTR2100049142).

Neurohormonal Profiles of Assistance Dogs Compared to Pet Dogs: What Is the Impact of Different Lifestyles?

Simple SummaryDogs are currently involved in various roles in our society beyond companionship. The tasks humans assign to them impact their daily life and can sometimes create stressful situations, possibly jeopardizing their welfare. For example, assistance dogs need to manage their emotions in various challenging situations and environments. Thus, the capacity to cope with emotional stress is highly desirable in assistance dogs (~40% of assistance dogs fail to complete their education program). The emotional and stress responses are guided by brain processes involving neuromodulators. Neurohormonal profiling of these dogs can: (i) give cues about their emotional suitability to fulfill an assistance role; (ii) enhance their selection; and (iii) help to assess and improve their welfare state during the training course. We compared basal blood levels of three neuromodulators of interest between two populations, assistance vs. pet dogs. We found significantly different concentrations of oxytocin, a neuromodulator involved in social behavior. Levels of prolactin, a putative marker of chronic stress, were higher (although not statistically significant) and variable in assistance dogs. Dogs’ age also seemed to influence the various neuromodulators levels. These findings highlight the impact of different lifestyles undergone by dogs and the possibility to use neurohormonal profiling to monitor their effect on the dogs’ welfare and stress state.Assistance dogs must manage stress efficiently because they are involved in challenging tasks. Their welfare is currently a fundamental issue. This preliminary study aimed to compare assistance dogs (AD; n = 22) with pet dogs (PD; n = 24), using blood neuromodulator indicators to help find biomarkers that can improve the AD breeding, selection, training, and welfare monitoring. Both populations originated from different breeds, are of different ages, and had different lifestyles. Basal peripheral concentrations of prolactin (PRL), serotonin (5-HT), free (fOT) and total (tOT) oxytocin were measured by immunoassays. Multiple linear regressions were performed to assess the effect of activity, age, sex, and their interactions on these parameters. Correlations between neurohormonal levels were analyzed. No interactions were significant. fOT and tOT concentrations were significantly influenced by age (p < 0.0001 and p = 0.0002, respectively) and dogs’ activity (p = 0.0006 and p = 0.0277, respectively). A tendency was observed for age effect on PRL (p = 0.0625) and 5-HT (p = 0.0548), as well as for sex effect on tOT (p = 0.0588). PRL concentrations were heterogenous among AD. fOT and tOT were significantly but weakly correlated (Pearson’s r = 0.34; p = 0.04). Blood prolactin, serotonin, and oxytocin may represent biomarkers to assess workload and chronic stress-related responses in ADs and eventually improve their selection and training.

The effects of delta-9-tetrahydrocannabinol exposure on female menstrual cyclicity and reproductive health in rhesus macaques

To determine the dose-dependent effect of contemporary marijuana exposure on female menstrual cyclicity and reproductive endocrine physiology in a nonhuman primate model. Research animal study. Research institute environment. Adult female rhesus macaques (6-12 years of age; n = 8). Daily delta-9-tetrahydrocannabinol (THC) edible at medically and recreationally relevant contemporary doses. Menstrual cycle length (MCL), anti-Müllerian hormone, prolactin, basal follicle-stimulating hormone (FSH), estradiol (E2) and progesterone, luteinizing hormone (LH), and thyroid-stimulating hormone. The average before THC weight was 6.9 kg (standard deviation, 0.8), and at the highest THC dosing, the average weight was 7.2 kg (standard deviation, 0.8). With increasing THC dosing, MCL and FSH concentrations increased, while basal E2 concentration was stable. The average MCL concentration increased 4.0 days for each mg/7 kg/day of THC (95% CI, 1.4-6.6 days). Follicle-stimulating hormone concentration increased significantly with increasing THC dose, 0.34 ng/mL for each mg/7 kg/day of THC (95% CI, 0.14-0.57 ng/mL). No significant trends were observed between THC dosing and average basal progesterone, anti-Müllerian hormone, prolactin, LH, or thyroid-stimulating hormone concentrations. In rhesus macaques, a dose response toward increased MCL and basal FSH concentrations but plateau of basal E2 and LH concentrations was observed with increasing THC dosing, suggesting ovulatory dysfunction. Further studies are needed to determine the effects of a longer duration of exposure and whether the significant increase in MCL and FSH concentrations results in reduced fecundity.

Comparative Assessment of Thermotolerance in Dorper and Second-Cross (Poll Dorset/Merino × Border Leicester) Lambs.

Simple SummarySelection of animal breeds that are adapted to extreme climatic conditions may help to sustain livestock production in the face of climate change. We measured the thermotolerance of 4–5-month-old Dorper and second-cross lambs (Poll Dorset × (Border Leicester × Merino)) by assessing feed intake, physiological, blood biochemical and prolactin responses. Heat stress reduced feed intake only in second-cross lambs but not in Dorpers. As expected, heat stress also increased water intake, respiration rate, rectal temperature, and skin temperature in both genotypes, but to a lesser extent in Dorpers. The comparatively lower influence of heat stress on thermotolerance indices in Dorper indicates adaptability of this breed to heat challenge.The objective of this study was to compare the thermotolerance of second-cross (SC; Poll Dorset × Merino × Border Leicester) and Dorper lambs. Dorper and SC lambs (4–5 months of age) were subjected to cyclic heat stress (HS) (28–40 °C). The temperature was increased to 38–40 °C between 800 and 1700 h daily and maintained at 28 °C for the remainder of the day (30–60% relative humidity (RH)) in climatic chambers for 2 weeks (n = 12/group), with controls maintained in a thermoneutral (TN) (18–21 °C, 40–50% RH) environment (n = 12/group). Basal respiration rate (RR), rectal temperature (RT) and skin temperature (ST) were higher (p < 0.01) in SC lambs than in Dorpers. HS increased RR, RT and ST (p < 0.01) in both genotypes, but the levels reached during HS were lower (p < 0.01) in Dorpers. HS increased (p < 0.01) water intake to a greater extent in SC lambs, while feed intake was reduced (p < 0.05) by HS in SC lambs but not in Dorpers. HS increased (p < 0.01) blood urea nitrogen and creatinine in SC lambs only. Plasma non-esterified fatty acid concentrations were reduced (p < 0.05) by HS in SC lambs but increased (p < 0.05) in Dorpers. There was no effect of HS on pO2, cHCO3− and cSO2, but higher (p < 0.01) blood pH and lower (p < 0.01) pCO2 were recorded under HS in both genotypes. Blood electrolytes and base excess were reduced (p < 0.01) under HS, while a genotype difference (p < 0.05) was only observed in blood K+ and hemoglobin concentrations. Basal plasma prolactin concentrations were lower (p < 0.01) in Dorpers but were elevated at a similar level during HS (p < 0.01) in both genotypes. Dorper lambs are more resilient to HS than SC lambs. Future research should focus on confirming whether the better heat tolerance of Dorpers is translated to better returns in terms of growth performance and carcass traits over the summer months.

SAT-247 Use of Double Dopamine Agonists in Giant Prolactinomas: A Series of 6 Cases

Dopamine agonist monotherapy is first line therapy in giant prolactinomas even when visual field defect is present. The costlier cabergoline is often preferred over bromocriptine due to higher efficacy and tolerability profile. Described herein combined cabergoline and bromocriptine therapy in 6 cases of giant prolactinomas. Retrospective records review of 6 patients with giant prolactinoma (3 males: M1-M3, 3 females: F1-F3) in a single tertiary centre was performed. Mean age at diagnosis: 29 years (range 17-39). Mean duration of follow up: 7 years (range 3-11). Headache and visual field defect were the presenting symptoms in all cases. Basal prolactin concentration: 100000 to 468851 mIU/L (<300 for male, <600 for female). Three patients have hypopituitarism at presentation, one after surgery and one remained eupitary 5 years after diagnosis. One developed late onset hypopituitarism 4 years after normalisation of prolactin levels. Three patients underwent debulking at presentation because of significant mass effects with obstructive hydrocephalus. In all patients cabergoline 1-1.5 mg/wk was started at diagnosis and gradually increased to 0.5 mg daily, aiming for normoprolactinemia. From May 2017 bromocriptine were given to these patients who continued to have hyperprolactinemia despite cabergoline 3.5-4mg/wk. Bromocriptine was commenced 1.25-5mg/day and gradually increased to 10 mg/day on top of cabergoline with careful monitoring of prolactin levels and side effects. Cabergoline was tapered down to 1.5-2mg/wk if prolactin levels remained stable between 2-3x normal while maintaining dose of bromocriptine. In M1, cabergoline was tapered off while maintaining bromocriptine 10mg/day with stable prolactin levels (~1000 mIU/L). In M2, normoprolactinemia was achieved after adding on bromocriptine and is currently on cabergoline 2mg/week and bromocriptine 10mg/day. In M3, whose prolactin were 4x normal value despite cabergoline 3.5mg/week, decreased 50% with bromocriptine 5 mg/day and remained stable when cabergoline reduced to 1.5mg/week. F1 had transphenoidal section twice due to failure of medical therapy. Her prolactin remained markedly elevated 10000-20000 mIU/L despite cabergoline 3.5 mg/week and bromocriptine 10mg/day, with persistent bitemporal hemianopia. F2 developed erythema nodosum after starting bromocriptine which was stopped and continued with cabergoline 1 mg/week. F3 showed partial response with 50% reduction in prolactin to 4485 mIU/L with bromocriptine 10 mg/day and cabergoline 1.5mg/week. In patients who underwent debulking, residual tumour remained unchanged. Two patients - tumour shrank 40% (F2) and 90% (M3) with medical therapy alone. In conclusion, adding on bromocriptine can be considered when high dose cabergoline is required for treatment of giant prolactinoma with careful monitoring. This reduces cabergoline dose which saves cost.

SAT-474 Giant Prolactinoma Case Series Assessing Response on Initial Dose of Cabergoline

Background: Giant prolactinomas (GPs) are rare representing 2-3% of prolactinomas and only ~ 0.5% of all pituitary tumors. Various definitions have been proposed for GP but commonly accepted criteria is tumor dimension of ≥4 cm. GP is often associated with very high prolactin (PRL) ranging 1,000 -100,000 ng/ml, significant extrasellar extension and no concomitant growth hormone or ACTH secretion. Patients predominantly present with neurological symptoms rather than endocrine dysfunction, and so the primary goal of treatment is amelioration of neurological symptoms. The literature search reveals approximately 190 papers on this topic and most are single case reports or series describing only unusual clinical manifestations. Hence, evidence based recommendations for treatment are lacking. Dopamine agonist (DA) is considered first line of therapy, as these tumors are highly sensitive to medical therapy. Surgery and radiation may be warranted in special situations. Low starting doses of cabergoline (CAB) are generally recommended due to concern for complications of apoplexy and cerebrospinal fluid (CSF) leak from rapid tumor shrinkage. However, no recommendations for a specific starting dose exist. Objective: Individual tumor and hormonal response were assessed on 15 patients (pts) with GP on low dose CAB; 0.25-0.5 mg weekly to determine the effectiveness of DA therapy. Methods: 15 GP pts from two tertiary care centers, meeting the diagnostic criteria mentioned above, were reviewed. Reduction in tumor volume and maximal tumor diameter along with PRL, after initiation of CAB, at or before 6 months and 1 year post diagnosis, was calculated. Results: Presenting symptom: visual disturbance (56%), headache (20%), apoplexy (13%) and incidental finding (6%). Mean age at diagnosis: 61 years. Male to Female: 4: 1. Basal prolactin concentration: >2000 ng/dl (12/15pts), and > 900 ng/ml (2/15). Initial total CAB dose/week: 0.25-0.5 mg (13/15) and 1-2 mg (2/15). Cranial surgery: 4/15. Complications: CSF leak (1/15). Tumor volume assessed at 6 months (11/15) and 1 year (4/15) along with decrease in maximum tumor diameter in the same period of time. PRL assessed at or before 6 months (13/15) and at 1 year (2/15). Improvement in tumor size occurred promptly even with low dose CAB (0.25-0.5mg/week). 100% of patients initiated on low dose CAB responded to therapy. Mean reduction in tumor volume at or before 6 months was 47% in 11/15, and 52% at 1 year (10/15). Mean decrease in maximal tumor dimension was calculated as 0.95 cm at 6 months (12/15) and 1.4 cm at 1 year (9/15). The overall prolactin response rate at or before 6 months was > 90% in 7/15 patients (53%) and >50% in 11/15 patients (73%). Conclusion: Our data confirms excellent tumor response to low dose cabergoline therapy. Dose as low at 0.25 mg twice weekly is proven to be effective, leading to decrease in both tumor volume and PRL levels.

Effect of 17β-estradiol on milk production, hormone secretion, and mammary gland gene expression in dairy cows

Estradiol inhibits milk production in dairy cows. The present study evaluated the effect of 17β-estradiol (E2) injections on prolactin (PRL) secretion and the mammary gland response to this hormone. Eight mid-lactation cows were used in a crossover design. During each experimental period, the cows were injected daily with either E2 (2.5 mg) or soy oil (2.5 mL; control) for 7 d. For each period, blood and milk samples were collected from d -4 to 14 (relative to the first injection) to measure PRL, insulin-like growth factor-1, and cortisol concentrations. In addition, blood samples were collected during morning milking on d -4, 2, and 7 to determine the milking-induced PRL release. Mammary gland biopsies were collected on the last day of injections. Milk fat samples were collected from d 1 to 7 and on d 14. The mRNA levels of genes encoding proteins related to mammary activity (α-lactalbumin, β-casein, and acetyl-coenzyme A carboxylase), apoptosis (Bax, Bcl2, and caspase-3), PRL receptors (PRLR; long and short forms), signal transducer and activator of transcription 5 (STAT5A and STAT5B), and suppressors of cytokine signaling (SOCS2 and SOCS3) were evaluated by real-time reverse transcription PCR using RNA extracted from milk fat and mammary biopsies. Milk production was decreased moderately (about 9%) by E2 injections during the treatment period. Estradiol injections increased basal PRL levels in serum and milk but did not affect milking-induced PRL release. Estradiol injections increased the plasma concentration of insulin-like growth factor-1 but did not affect cortisol concentration during the treatment period. In mammary tissue, the expression of Bcl2 was downregulated, whereas that of STAT5A and B and the Bax:Bcl2 mRNA ratio was higher during E2 injections. The total STAT5 protein content in mammary tissue was elevated by E2 injections. We found no significant difference observed for the other genes in mammary tissue or milk fat. The present data do not support the contention that E2 injections inhibit milk production by interfering with PRL signaling, but enhanced basal PRL concentration and STAT5 gene expression in mammary tissue.

Seasonal Assessment of Duration of Prolactin Suppression Following Cabergoline Treatment in Mares: Unstimulated Versus Sulpiride and Thyrotropin-Releasing Hormone-Stimulated Responses

Experiments 1 through 4 were performed to test the hypothesis that season affects the duration of prolactin suppression by a single injection of the dopaminergic agonist, cabergoline. In each, six mares received cabergoline intramuscularly and four received the vehicle. The protocol was repeated around the vernal equinox, summer solstice, autumnal equinox, and winter solstice. In all experiments, cabergoline suppressed (P < .01) prolactin for at least 5 days; concentrations in fall and winter were naturally low; thus, treatment effects were harder to detect. Experiments 5 and 6 tested whether basal (unstimulated) prolactin concentrations recovered from cabergoline suppression faster (earlier) than secretagogue-induced prolactin secretion. In July, five mares each were treated with either compounded cabergoline or cabergoline in oil; four others received oil. Cabergoline suppressed (P < .0001) prolactin in both treated groups for approximately 6 days. Prolactin in daily samples returned to control levels thereafter, whereas low-dose sulpiride-stimulated secretion remained suppressed by >50% at 11 days after treatment. In the last experiment, treatment with cabergoline or oil (n = 6 mares each) in October followed by thyrotropin-releasing hormone (TRH) challenges resulted in similar responses to those in experiment 5; TRH-induced prolactin responses were still suppressed (P < .05) on day 11. In conclusion, little seasonal variation in duration of prolactin suppression in response to cabergoline was detected. In general, secretagogue-induced secretion is suppressed much longer than basal secretion. This dichotomy may indicate at least two subpopulations of lactotropes regulated differentially by dopamine input.

Consumption of endophyte-infected fescue seed during the dry period does not decrease milk production in the following lactation

Ergot alkaloids in endophyte-infected grasses inhibit prolactin (PRL) secretion and may reduce milk production of cows consuming these grasses. We investigated the effects of consuming endophyte-infected fescue seed during late lactation and the dry period on mammary growth, differentiation, and milk production. Twenty-four multiparous Holstein cows were randomly assigned to 3 treatment groups. Starting at 90±4 d prepartum, cows were fed endophyte-free fescue seed (control; CON), endophyte-free fescue seed plus 3×/wk subcutaneous injections of bromocriptine (0.1mg/kg of body weight, positive control; BROMO), or endophyte-infected fescue seed (INF) as 10% of the diet on an as fed basis. Although milk yield of groups did not differ before treatment, at dry off (−60 d prepartum) INF and BROMO cows produced less milk than CON. Throughout the treatment period, basal concentrations of PRL and the prepartum increase in plasma PRL were reduced in INF and BROMO cows compared with CON cows. Three weeks after the end of treatment, circulating concentrations of PRL were equivalent across groups. In the subsequent lactation milk yield was not decreased; in fact, BROMO cows exhibited a 9% increase in milk yield relative to CON. Evaluation of mammary tissue during the dry period and the subsequent lactation, by quantitative histology and immunohistochemical analysis of proliferation markers and putative mammary stem or progenitor cell markers, indicated that feeding endophyte-infected fescue seed did not significantly affect mammary growth and development. Feeding endophyte-infected grasses during the dry period may permit effective utilization of feed resources without compromising milk production in the next lactation.

The dopamine antagonist domperidone increases prolactin concentration and enhances milk production in dairy cows

In previous studies, our team showed that the inhibition of prolactin (PRL) secretion by the dopamine agonist quinagolide reduces milk production in dairy cows. The objective of this study was to determine the effects of administration of a dopamine antagonist on basal and milking-induced PRL concentrations in blood and on milk production during positive energy balance and feed restriction in dairy cows. Eighteen mid-lactation Holstein cows received daily s.c. injections of either domperidone (300mg, DOMP, n=9) or the vehicle, canola oil (CTL, n=9), for 5wk. During wk 5, all cows were fed at 65% of their dry matter intake in the previous week. Blood and milk samples were collected before (for blood) and during (for milk) the a.m. milking thrice weekly from d −9 to 41 (8d after the last injection). In addition, blood samples were collected during the a.m. milking on d −1 (before the first injection), and on d 1, 28, and 34. Basal PRL concentration was similar in both groups before the start of the treatments. Domperidone injections caused a gradual increase in basal PRL concentration. Feed restriction reduced basal PRL concentration in both the CTL and DOMP cows, but PRL concentration remained higher in the DOMP cows. Prolactin concentration remained elevated in the DOMP cows 7d after the last injection. The milk concentration of PRL increased during the DOMP treatment, but the increase was smaller than that observed in serum. In the CTL cows, the milking-induced PRL release above the premilking concentration was similar on d −1, 1, and 28 but was reduced during feed restriction. In the DOMP cows, the milking-induced PRL release was similar on d −1 and 1 but was reduced on d 28 and 34. Milk production was similar for both groups before the treatments started but was greater in the DOMP cows during the treatment period, at 2.9±0.6 and 2.4±0.6kg/d greater during wk 3 and 4 of treatment, respectively. Milk production declined in both groups during feed restriction but remained higher in the DOMP cows. Milk production became similar again for both groups after the last injection. In addition, dry matter intake was increased by DOMP. These results support the hypothesis that PRL is galactopoietic in dairy cattle.

Effects of hypothalamic dopamine (DA) on salsolinol (SAL)‐induced prolactin (PRL) secretion in male goats

The aim of the present study was to clarify the effects of hypothalamic dopamine (DA) on salsolinol (SAL)-induced prolactin (PRL) release in goats. The PRL-releasing response to an intravenous (i.v.) injection of SAL was examined after treatment with augmentation of central DA using carbidopa (carbi) and L-dopa in male goats under 8-h (8 h light, 16 h dark) or 16-h (16 h light, 8 h dark) photoperiod conditions. The carbi and L-dopa treatments reduced basal PRL concentrations in the 16-h photoperiod group (P < 0.05), while a reduction was not observed in the 8-h photoperiod group. The mean basal plasma PRL concentration in the control group for the 8-h photoperiod was lower than that for the 16-h photoperiod (P < 0.05). SAL significantly stimulated the release of PRL promptly after the injection in both the 8- and 16-h photoperiod groups (P < 0.05). PRL-releasing responses for the 16-h photoperiod were greater than those for the 8-h photoperiod (P < 0.05). The carbi and L-dopa treatments blunted SAL-induced PRL release in both the 8- and 16-h photoperiods (P < 0.05). These results indicate that hypothalamic DA blunts the SAL-induced release of PRL in male goats, regardless of the photoperiod, which suggests that both SAL and DA are involved in regulating the secretion of PRL in goats.

Late Primary Autoimmune Hypothyroidism in a Patient with Postdelivery Autoimmune Hypopituitarism Associated with Antibodies to Growth Hormone and Prolactin-Secreting Cells

Pituitary and thyroid autoimmunity can be triggered by pregnancy. We report the first association of combined growth hormone (GH) and prolactin secretion deficiency due to autoimmune damage to GH- and prolactin-secreting cells in a patient with postdelivery lactation failure, presenting subsequently with primary autoimmune hypothyroidism. A 34-year-old woman presented with lactation failure following the delivery of her first child. She had a family history of hypothyroidism without a history of pituitary dysfunction. Physical examination did not show any abnormal findings. Laboratory investigations showed normal gonadotropin levels after the restoration of normal menstrual cycles following pregnancy, normal basal and stimulated cortisol levels, but an impaired GH response to insulin-induced hypoglycemia, and low basal prolactin and insulin-like growth factor-1 concentrations. Thyroid function was normal when initially investigated three months after delivery, but five months later, marked primary hypothyroidism (thyrotropin levels >100 mIU/L) occurred. Immunological investigation revealed the presence of antipituitary antibodies, identified by double immunofluorescence and targeting GH- and prolactin-secreting cells. Antithyroid antibodies, in the normal range three months postpartum, became significantly elevated when the hypothyroidism appeared. Autoimmune hypophysitis is responsible for selective or multiple pituitary-hormone deficiencies, sometimes involving thyrotropin secretion and causing secondary hypothyroidism, but usually associated with hyperprolactinemia. To our knowledge, this is the first observation of autoimmune hypopituitarism involving deficient growth hormone and prolactin secretion in a patient with lactation failure after delivery, subsequently followed by severe primary autoimmune hypothyroidism, thus falling into an unusual constellation of autoimmune polyendocrine syndrome type 3. Considering the well-known relationship between pregnancy and autoimmunity, an early postdelivery immunological and functional investigation in women presenting with disorders of lactation may be useful to detect potential pituitary and thyroid dysfunction even at a subclinical stage.

Effects of melatonin on salsolinol‐induced prolactin secretion in goats

The aim of the present study was to clarify the effect of melatonin (MEL) on the salsolinol (SAL)-induced release of prolactin (PRL) in goats. Female goats were kept at 20°C with 16 h of light, 8 h of darkness, and orally administered saline or MEL for 5 weeks. A single intravenous (i.v.) injection of saline (controls), SAL, thyrotropin-releasing hormone (TRH) or a dopamine receptor antagonist, sulpiride, was given to the goats 3 weeks after the first oral administrations of saline or MEL, and the responses were compared. The mean basal plasma PRL concentrations in the control group were higher for the saline treatments than MEL treatments (P < 0.05). SAL as well as TRH and sulpiride stimulated the release of PRL promptly after each injection in both the saline- and MEL-treated groups (P < 0.05). The area under the response curve of PRL for the 60-min period after the i.v. injection of SAL, TRH and sulpiride in the saline-treated group was greater than each corresponding value in the MEL-treated group (P < 0.05). These results show that daily exposure to MEL under a long day length reduces the PRL-releasing response to SAL as well as TRH and sulpiride in goats.

Effect of prolactin-release inhibition on milk production and mammary gland involution at drying-off in cows

The end of each lactation is a challenging period for high-yielding cows as they are often dried off while still producing significant quantities of milk and, consequently, are highly susceptible to new intramammary infections. Once involution is complete, the mammary gland becomes much more resistant to infection. Therefore, it is critically important to develop strategies aimed at reducing milk production before drying-off and to accelerate mammary gland involution. This study assessed the effect of inhibition of the lactogenic signal driven by prolactin (PRL) on milk production and concentrations of involution markers in mammary secretions. Sixteen Holstein cows in late lactation were assigned to treatments based on milk yield, somatic cell count, and parity. Of those cows, 8 received twice-daily intramuscular injections (2mg per injection) of quinagolide, a specific inhibitor of PRL release, from 4d before drying-off to 3d after (Quin). The other 8 cows received injections of the solvent (water, control). Blood and milk (mammary secretion) samples were collected on the last 5d before and on d 1, 3, 5, 7, 10, and 14 after the last milking. Additionally, on the day preceding the first injection and on the following day, several blood samples were collected around milking time. Quinagolide reduced basal serum PRL concentrations on all injection days as well as PRL released in blood during milking. The PRL inhibitor decreased milk production before drying-off, which averaged, over the last 3d of lactation, 19.3 and 15.5kg/d for the control and Quin cows, respectively. Quinagolide had no significant effect on milk citrate:lactoferrin and Na:K ratios, which decreased and increased, respectively, during the first 2wk of the dry period. Nevertheless, the increases in the number of somatic cells and bovine serum albumin concentration during early involution were greater and matrix metalloproteinase-2 activity tended to be greater in mammary secretions of the Quin cows compared with the control cows. This experiment shows that inhibition of PRL release decreases milk production of cows in late lactation. Changes in the composition of mammary secretions suggest that this approach also hastens mammary gland involution.

Poor positioning, decreased prolactin levels, and low milk output associated with early cessation of exclusive breastfeeding in obese women

High prepregnant maternal body mass index (BMI) is associated with reduced breastfeeding duration. The objective of this research was to examine how maternal obesity might impact early cessation of exclusive breastfeeding (EBF) by exploring key aspects of early breastfeeding success: prolactin values, milk output, and mother‐infant positioning during the first week postpartum. In this prospective study, data were collected from 51 primiparous women from Minnesota. Multivariate models were used to determine relationships between maternal obesity and early cessation of EBF via a variety of breastfeeding outcome variables. Among overweight and obese women, 35% stopped breastfeeding exclusively by 2 weeks postpartum compared to 4% of normal BMI women (P &lt; 0.05). Greater milk output at 1 week postpartum reduced the risk of early cessation of EBF (OR 0.41, P &lt; 0.05). Milk output was significantly associated with the predictor variables of basal prolactin concentration within 48 hours postpartum (P &lt; 0.05) and Mother‐Baby Assessment (MBA) score (a measure of efficient positioning) at 1 week postpartum (P &lt; 0.0001). Prolactin levels (P &lt; 0.05) and MBA scores (P &lt; 0.05) were in turn negatively associated with maternal obesity. These findings suggest that low milk output, influenced by decreased prolactin levels and especially poor positioning, may play a role in early cessation of EBF among obese women. Funded by NSF.

Effect of the prolactin-release inhibitor quinagolide on lactating dairy cows

In most mammals, prolactin (PRL) is essential for maintaining lactation, and yet the short-term suppression of PRL during established lactation by bromocriptine has produced inconsistent effects on milk yield in cows and goats. To assess the effect of the long-term inhibition of PRL release in lactating dairy cows, 5 Holstein cows in early lactation received daily intramuscular injections of 1mg of the PRL-release inhibitor quinagolide for 9 wk. Four control cows received the vehicle (water) only. During the last week of the treatments, one udder half was milked once a day (1×) and the other twice a day (2×). Blood samples were harvested at milking in wk −1, 1, 4, and 8. The daily injections of quinagolide reduced milking-induced PRL release but not the basal PRL concentration. Quinagolide induced a faster decline in milk production, which was about 5.3kg/d lower in the quinagolide-treated cows during the last 4 wk of treatment. During wk 9, the inhibition of milk production by quinagolide was maintained in the udder half that was milked 2× but not in the half milked 1×. Milk production was significantly correlated with the quantity of PRL released at milking. Quinagolide did not affect the release of oxytocin at milking. Serum concentration of insulin-like growth factor-1 was not affected by treatment or correlated with milk production. Serum concentrations of leptin and the calciotropic hormone stanniocalcin were not affected by the treatment. In conclusion, the chronic administration of the PRL-release inhibitor quinagolide decreases milk production in dairy cows. The effect is likely the result of the reduced release of milking-induced PRL and is modulated at the level of the gland by milking frequency.

Prolactin response to suckling in a group of fully breast feeding women during the early postpartum period.

Prolactin response to suckling was studied in a group of fully breast feeding women (N = 58) between 4-6 weeks postpartum. Basal, suckling stimulated and the increment of prolactin showed wide individual variations. Basal prolactin concentrations varied from 140 to 4,600 mIU/l, suckling stimulated prolactin from 400 to 5,600 mIU/l and the increment of prolactin from 40 to 4,160 mIU/l. Basal (p = 0.0395) and suckling stimulated (p = 0.0423) prolactin concentrations significantly increased as the number of night breast feeds increased and the suckling stimulated (p = 0.0218) prolactin concentrations significantly increased as the number of breast feeds/24 h increased. However, the magnitude of the rise in prolactin in response to suckling was not dependent on basal prolactin concentration. Basal, suckling stimulated or the increment of prolactin were not significantly different between subjects having different breast feeding frequencies, when the subjects were grouped according to the number of breast feeds. These differences may be due to the large individual variation in prolactin concentrations seen in women having similar breast feeding frequencies which may arise from individual variations in hypothalamic--pituitary response to suckling.

Concentrations of Prolactin, LH, Testosterone, TSH and Thyroxine in Normospermic Dogs of Different Breeds

Concentrations of prolactin (PRL), LH, testosterone (T), TSH and thyroxine (T(4)) were determined before and at 20, 120 and 180 min after a single iv injection of thyrotropin-releasing hormone (TRH) in eight Beagles, eight Fox Terriers, six Labrador Retrievers and five Great Danes that were normospermic. Mean basal PRL concentrations were lower in the Fox Terriers compared with the Great Danes (p < 0.05). Mean LH concentrations were higher in the Fox Terriers than in the Beagles, and T was lower in the Fox Terriers at some times but not others (p < 0.05). Thyroid Stimulating Hormone (TSH) concentrations did not differ among breeds, while mean basal T(4) values were lower in Fox Terriers compared with Labrador Retrievers and Great Danes (p < 0.05). Stimulation of T(4) secretion 120 and 180 min after iv TRH injection was most pronounced in the Beagles and less in the Fox Terriers (p < 0.05). The results of the present study indicate that potential breed differences in circulating concentrations of PRL, LH, T, TSH and T(4) in male dogs with apparently normal fertility can be encountered, but further studies are needed to determine whether the observed differences are typical features of these breeds, reflect subsets of dogs within breeds, or are in part because of possible uncontrolled parameters such as sample timing, ambient photoperiod, housing conditions or diet.

Medical Therapy in Patients with Acromegaly: Predictors of Response and Comparison of Efficacy of Dopamine Agonists and Somatostatin Analogues

Acromegaly is associated with increased morbidity and mortality. Treatment options include surgery, radiotherapy, and medical therapy. The objective of the study was to examine the role of prolactin status, prior surgery, and radiotherapy on the response to medical therapy in patients with acromegaly and assess the relative efficacy of dopamine agonist therapy compared with somatostatin analog therapy. A total of 276 patients with acromegaly received either dopamine agonists (DA) and/or somatostatin analogs (SSA). One hundred seventy-two patients had received surgery and 73 radiotherapy prior to receiving medical therapy. One hundred ninety-eight of 276 received DA, and 143 of 276 received SSA. GH and IGF-I values at baseline and after 12 months on therapy were analyzed. In the DA group, basal prolactin concentration did not predict response to therapy, GH percent reduction: hyperprolactinemia, 26.7% (-10.4 to 48) vs. normoprolactinemia, 34.8% (0.2-53.2), P = 0.58; IGF-I percent reduction: hyperprolactinemia 30.0% (9.2-43.1) vs. normoprolactinemia 16.8% (4-37), P = 0.45. Prior surgery was not associated with any difference in response to DA: GH percent reduction (P = 0.1) and IGF-I percent reduction (P = 0.08). By contrast, prior radiotherapy was associated with an enhanced efficacy of GH response to DA, P = 0.02. In the SSA group, there was no effect of prior surgery or radiotherapy on response of GH, but radiotherapy was associated with less marked IGF-I percent reduction (P = 0.05). SSA were more potent than DA at decreasing both GH [62.8% (20.7-85%) vs. 42.4% (-6.5 to 68.6), P < 0.008] and IGF-I [SSA 40.4% (0-64.3) vs. 8% (0-40.8), P = 0.05]. The effects of DA are irrespective of baseline prolactin concentrations. Prior radiotherapy is associated with differences in GH and IGF-I response to DA and SSA therapy.

Influence of modified transdermal hormone replacement therapy on the concentrations of hormones, growth factors, and bone mineral density in women with osteopenia

The metabolic and therapeutic action of estrogens depends on their type, dosage, form, route of administration, and treatment-free interval during the therapeutic cycle. Hormone therapy is generally subclassified into 2 forms that differ in the type of hormones. In hormonal replacement therapy (HRT), estrogens and progesterone components do not differ in chemical structure and molecular mass from those naturally produced by the female organism. In hormonal supplementary therapy (HST), the estrogen and progestagen components do differ from the natural hormones in structure and mass. The aim of the study was to compare 2 kinds of hormonal therapy in early postmenopausal women with osteopenia. These forms of therapy are modified transdermal HRT and orally given HST. The objective of this study was the estimation of sex hormone, insulin-like growth factor I (IGF-I), prolactin (PRL), osteocalcin, and procollagen concentration in serum as well as the degree of mineralization of the lumbar spine in women in the early postmenopausal period with osteopenia under different kinds of hormonal therapy. The study was conducted in 75 women with an average age of 52.4 ± 3.5 years and with primary osteopenia, in the early postmenopausal period, who were randomly assigned to 3 groups depending on the form and route of administration of therapy: Group I (n = 25, control) was receiving placebo in the form of patches. Group II (n = 25) was treated with modified transdermal HRT. This group obtained micronized 17 β-estradiol at increasing-decreasing doses and progesterone in the second phase of the therapeutic cycle. Group III (n = 25) was receiving orally given HST and obtained Cyclo-Menorette (Wyeth, Munster, Germany). The therapeutic cycle in each group lasted 21 days, followed by a 7-day medication-free interval. Estradiol concentration in serum was increased 5-fold and estrone (E 1) was increased about 11-fold in the group of women receiving orally given HST ( P < .0001) compared with control group. Estrone and estradiol levels were increased about 3-fold in women receiving modified transdermal HRT compared with the baseline values. Basal PRL concentration and PRL level after metoclopramide stimulation test significantly increased after 3 and 12 months of treatment in the group receiving orally given HST. In women receiving modified transdermal HRT, increased IGF-I concentrations were statistically significant after 3 months of treatment. In the group of women receiving orally given HST, a significant decrease of IGF-I after 1 year therapy was found. During the entire time of treatment in this group, an increase of growth hormone was observed. No significant changes were shown in osteocalcin and in carboxyterminal propeptide of type I procollagen in all groups. Increase in bone mineral density L 2-L 4 was statistically significant in the group receiving modified transdermal HRT ( P < .01) and was insignificant in women receiving orally given HST after 12 months of therapy as compared with baseline values. Following are the conclusions: (1) Low-dose modified transdermal HRT modulates concentration of hormones, growth factor, IGF-I, osteocalcin, procollagen, and bone metabolism. (2) The curve concentrations of estrogens and progesterone in serum are similar to the type observed in the physiologic menstrual cycle. (3) The lack of significant increase in bone mineral density of lumbar spine in women after HST may be a result of significantly lower concentration of IGF-I in serum and occurring hyperprolactinemia.