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Journal of Neuroendocrinology Apr 2024The conserved and multifaceted functions of prolactin (PRL) are coordinated through varied distribution and expression of its cell-surface receptor (PRLR) across a range... (Review)
Review
The conserved and multifaceted functions of prolactin (PRL) are coordinated through varied distribution and expression of its cell-surface receptor (PRLR) across a range of tissues and physiological states. The resultant heterogeneous expression of PRLR mRNA and protein across different organs and cell types supports a wide range of PRL-regulated processes including reproduction, lactation, development, and homeostasis. Genetic variation within the PRLR gene also accounts for several phenotypes impacting agricultural production and human pathology. The goal of this review is to highlight the many elements that control differential expression of the PRLR across tissues, and the various phenotypes that exist across species due to variation in the PRLR gene.
PubMed: 38586906
DOI: 10.1111/jne.13385 -
Endocrine Apr 2024Men with macroprolactinoma can present persistent hypogonadism despite normoprolactinemia achieved with clinical and/or neurosurgical treatment. Usually, testosterone...
BACKGROUND
Men with macroprolactinoma can present persistent hypogonadism despite normoprolactinemia achieved with clinical and/or neurosurgical treatment. Usually, testosterone replacement therapy is indicated. Nevertheless, although off-label, clomiphene citrate (CC), a selective estrogen receptor modulator, has also been used, mainly when fertility is an issue. The aim of this study is to evaluate the effectiveness of CC in recovering the gonadal axis in men with macroprolactinoma, with or without hyperprolactinemia, and evaluate its safety as a long-term therapy.
METHODS
This is a retrospective study including 10 men with macroprolactinoma on cabergoline treatment and persistent hypogonadism. All patients received initially 50 mg/d of CC.
RESULTS
The median age at diagnosis of prolactinomas was 34 (range, 26-60) years old. All patients were treated with cabergoline at a median maximum dose of 2 (1-7) mg/week, with a median time of treatment of 8.5 (2-15) years. Prolactin was still above the normal range when CC was introduced only in two patients. The mean duration of CC therapy was 3.2 (±2.8) years. Prolactin levels maintained stable (p = 0.252) and testosterone increased (p = 0.027) significantly on CC therapy. Tumor size remained stable. Eight patients (80%) maintained testosterone above 300 ng/dL and were classified as responders. Three responders succeeded in using a lower dose of CC and one of them completed withdrawal CC and maintained eugonadism. There were no side effects or safety concerns reported.
CONCLUSION
CC should be seen as a safe treatment option for men with macroprolactinoma and persistent hypogonadism.
PubMed: 38578401
DOI: 10.1007/s12020-024-03817-0 -
Breastfeeding Medicine : the Official... Apr 2024: Migraine attacks are common in women of reproductive age. Although attacks are often less severe and less frequent during pregnancy, they regularly reoccur shortly...
: Migraine attacks are common in women of reproductive age. Although attacks are often less severe and less frequent during pregnancy, they regularly reoccur shortly after delivery. When first-line analgesic treatment is insufficient, triptans may be used for acute treatment of migraine attacks. Milk levels of occasional triptan use have shown to be low, and no adverse effects in breastfed infants have been reported. However, the available knowledge on the safety of triptans during breastfeeding is still limited. Four (inter)national pharmacovigilance databases were searched for breastfeeding related adverse drug reactions of triptans. These included the Dutch Pregnancy Drug Register and three databases of spontaneous reports (Netherlands Pharmacovigilance Centre Lareb, the European Medicines Agency [EudraVigilance], and the World Health Organization [VigiBase]). A total of 26 reports on 27 breastfeeding related adverse drug reactions were identified (one report involved two separate adverse drug reactions). These involve three main complaints: painful breasts and/or nipples, painful milk ejection reflex, and a decrease in milk production. The hypothesized pharmacological mechanism relates to the serotonin-receptor agonistic properties of triptans. These may lead to vasoconstriction in the breasts and nipples, including the vasculature surrounding the milk ducts and alveoli, and may also influence the hormonal function and levels of prolactin. The reported adverse drug reactions do not negatively impact the overall compatibility of triptans with breastfeeding. However, breastfeeding women may experience them as unsettling. Awareness of these potential adverse drug reactions is essential and should be weighed against the potential adverse effects of (untreated) symptoms of migraine attacks.
PubMed: 38563407
DOI: 10.1089/bfm.2024.0022 -
Pharmacology, Biochemistry, and Behavior Jun 2024Pituitary lactotrophs are under tonic dopaminergic inhibitory control and bromocriptine treatment blocks prolactin secretion.
BACKGROUND
Pituitary lactotrophs are under tonic dopaminergic inhibitory control and bromocriptine treatment blocks prolactin secretion.
METHODS
Sleep and local field potential were addressed for 72 h after bromocriptine treatments applied during the different stages of the estrus cycle and for 24 h in the early- and middle postpartum period characterized by spontaneously different dynamics of prolactin release in female rats.
RESULTS
Sleep changes showed strong dependency on the estrus cycle phase of the drug application. Strongest increase of wakefulness and reduction of slow wave sleep- and rapid eye movements sleep appeared during diestrus-proestrus and middle postpartum treatments. Stronger sleep-wake effects appeared in the dark phase in case of the estrus cycle treatments, but in the light phase in postpartum treatments. Slow wave sleep and REM sleep loss in case of estrus cycle treatments was not compensated at all and sleep loss seen in the first day post-injection was gained further later. In opposition, slow wave sleep loss in the light phase after bromocriptine injections showed compensation in the postpartum period treatments. Bromocriptine treatments resulted in a depression of local field potential delta power during slow wave sleep while an enhancement in beta and gamma power during wakefulness regardless of the treatment timing.
CONCLUSIONS
These results can be explained by the interplay of dopamine D2 receptor agonism, lack of prolactin release and the spontaneous homeostatic sleep drive being altered in the different stages of the estrus cycle and the postpartum period.
Topics: Animals; Bromocriptine; Female; Postpartum Period; Rats; Receptors, Dopamine D2; Dopamine Agonists; Estrous Cycle; Rats, Wistar; Sleep; Wakefulness; Prolactin
PubMed: 38537873
DOI: 10.1016/j.pbb.2024.173754 -
Open Forum Infectious Diseases Mar 2024Astroviral infections commonly cause acute nonbacterial gastroenteritis in children globally. However, these infections often go undiagnosed outside of research...
BACKGROUND
Astroviral infections commonly cause acute nonbacterial gastroenteritis in children globally. However, these infections often go undiagnosed outside of research settings. There is no treatment available for astrovirus, and Astroviridae strain diversity presents a challenge to potential vaccine development.
METHODS
To address our hypothesis that host genetic risk factors are associated with astrovirus disease susceptibility, we performed a genome-wide association study of astrovirus infection in the first year of life from children enrolled in 2 Bangladeshi birth cohorts.
RESULTS
We identified a novel region on chromosome 1 near the loricrin gene () associated with astrovirus diarrheal infection (rs75437404; meta-analysis = 8.82 × 10; A allele odds ratio, 2.71) and on chromosome 10 near the prolactin releasing hormone receptor gene () (rs75935441; meta-analysis = 1.33 × 10; C allele odds ratio, 4.17). The prolactin-releasing peptide has been shown to influence feeding patterns and energy balance in mice. In addition, several single-nucleotide polymorphisms in the chromosome 1 locus have previously been associated with expression of innate immune system genes and .
CONCLUSIONS
This study identified 2 significant host genetic regions that may influence astrovirus diarrhea susceptibility and should be considered in further studies.
PubMed: 38524222
DOI: 10.1093/ofid/ofae045 -
Frontiers in Endocrinology 2024Ectopic thyroid-stimulating hormone (TSH)-secreting tumors are extremely rare, with only 15 reported cases in the literature. Herein, we described a 60-year-old female... (Review)
Review
Ectopic thyroid-stimulating hormone (TSH)-secreting tumors are extremely rare, with only 15 reported cases in the literature. Herein, we described a 60-year-old female patient with thyrotoxicosis and elevated or unsuppressed levels of TSH. Family history and laboratory and genetic tests did not support a diagnosis of resistance to thyroid hormone (RTH). Given the unsuppressed TSH, TSH-secreting tumor was suspected, and magnetic resonance imaging (MRI) of the pituitary gland was performed. Surprisingly, the MRI scans revealed a nodule in the nasopharynx rather than a pituitary tumor in the sella region. Further evaluation using Gallium-68 DOTATATE positron emission tomography/computed tomography (Ga-DOTATATE PET/CT) demonstrated increased DOTATATE uptake in the nasopharyngeal nodule. Additionally, an octreotide suppression test (OST) revealed an obvious reduction in TSH levels, further supporting the suspicion of the nasopharyngeal mass as the cause of inappropriate TSH secretion. To prepare for surgery, the patient received preoperative administration of octreotide, resulting in the normalization of TSH and thyroid hormone levels. The patient subsequently underwent successful surgical removal of the nasopharyngeal mass. Following the procedure, the patient experienced complete resolution of hyperthyroidism symptoms, with TSH declined and thyroid hormone levels returned to normal. Histochemistry analysis of the tumor revealed positive staining for TSH, growth hormone (GH), prolactin (PRL), luteinizing hormone (LH), and somatostatin receptor 2 (SSTR2). We discussed differential diagnosis of hyperthyroidism due to inappropriate TSH secretion, with a particular emphasis on the importance of Ga-DOTATATE PET/CT in combination with OST for identifying ectopic pituitary tumors.
Topics: Female; Humans; Middle Aged; Adenoma; Gallium Radioisotopes; Hyperthyroidism; Octreotide; Pituitary Neoplasms; Positron Emission Tomography Computed Tomography; Thyroid Hormones; Thyroid Neoplasms; Thyrotropin
PubMed: 38516415
DOI: 10.3389/fendo.2024.1301260 -
Veterinary Parasitology Jun 2024The physiologic increase in some sex hormones has been associated with an increase in the parasite load caused by Haemonchus contortus in ewes, especially prolactin. In...
The physiologic increase in some sex hormones has been associated with an increase in the parasite load caused by Haemonchus contortus in ewes, especially prolactin. In lambs that are especially susceptible to hemonchosis, the levels of sex hormones are low; in contrast, the levels of another pituitary hormone, growth hormone (GH), which is structurally very similar to prolactin, are high. In this study, the in vitro and in vivo effects of GH on H. contortus larvae development and establishment were evaluated. The addition of 20 ng/mL GH for 5 and 10 days to cultures of H. contortus larvae induced an enlargement (p<0.01) and an L3/L4 molting rate (p<0.03) greater than that of untreated larvae or those treated with other concentrations of the hormone. Flow cytometry showed that 3.8% of the largest and most complex cells of newly obtained larvae of H. contortus were positive for the GH receptor, and by immunofluorescence with confocal microscopy, it was observed that these receptors are located in the intestinal region larvae. In the in vivo assay, the administration of recombinant GH to gonadectomized lambs produced an increase in FEC (p<0.03), the number of female adult worms in the abomasum (p<0.05) and the levels of specific antibodies (p<0.04) in relation to the control lambs; however, it did not affect the fertility of H. contortus females. Although many factors affect the development and implantation of H. contortus in the abomasum of sheep, the results of this study strongly suggest that GH participates in the development and establishment of the parasite in sheep, mainly in young sheep.
Topics: Animals; Haemonchus; Sheep; Haemonchiasis; Sheep Diseases; Growth Hormone; Larva; Female; Male; Receptors, Somatotropin
PubMed: 38508098
DOI: 10.1016/j.vetpar.2024.110166 -
ACS Medicinal Chemistry Letters Mar 2024Neuromedin U receptor 2 (NMUR2), which is expressed in the central nervous system (CNS) including the hypothalamus, has been noted as a therapeutic target against...
Neuromedin U receptor 2 (NMUR2), which is expressed in the central nervous system (CNS) including the hypothalamus, has been noted as a therapeutic target against obesity. We previously reported that intranasal administration of CPN-219, a NMUR2-selective hexapeptide agonist, suppresses body weight gain in mice; however, there is no detailed information regarding its CNS effects. Recently, in addition to appetite suppression, stress responses and regulation of prolactin (PRL) secretion have also attracted attention. NMUR2 expressed in the hypothalamic tuberoinfundibular dopaminergic neurons has emerged as an alternative target for treating hyperprolactinemia. Here, CPN-219 decreased food intake up to 24 h after administration at a dose of 200 nmol, resulting in body weight gain suppression, although grooming and anxiety-like behaviors were transiently induced. Interestingly, the restraint stress-induced increase in plasma PRL levels was significantly suppressed at a lower dose of 20 nmol, indicating the potential for drug development as an anti-PRL agent of NMUR2-selective agonists.
PubMed: 38505846
DOI: 10.1021/acsmedchemlett.3c00541 -
BMC Genomics Mar 2024Muscle growth post-birth relies on muscle fiber number and size. Myofibre number, metabolic and contractile capacities are established pre-birth during prenatal...
BACKGROUND
Muscle growth post-birth relies on muscle fiber number and size. Myofibre number, metabolic and contractile capacities are established pre-birth during prenatal myogenesis. The aim of this study was to identify genes involved in skeletal muscle development in cattle, sheep, and pigs - livestock.
RESULTS
The cattle analysis showed significant differences in 5043 genes during the 135-280 dpc period. In sheep, 444 genes differed significantly during the 70-120 dpc period. Pigs had 905 significantly different genes for the 63-91 dpc period.The biological processes and KEGG pathway enrichment results in each species individually indicated that DEGs in cattle were significantly enriched in regulation of cell proliferation, cell division, focal adhesion, ECM-receptor interaction, and signaling pathways (PI3K-Akt, PPAR, MAPK, AMPK, Ras, Rap1); in sheep - positive regulation of fibroblast proliferation, negative regulation of endothelial cell proliferation, focal adhesion, ECM-receptor interaction, insulin resistance, and signaling pathways (PI3K-Akt, HIF-1, prolactin, Rap1, PPAR); in pigs - regulation of striated muscle tissue development, collagen fibril organization, positive regulation of insulin secretion, focal adhesion, ECM-receptor interaction, and signaling pathways (PPAR, FoxO, HIF-1, AMPK). Among the DEGs common for studied animal species, 45 common genes were identified. Based on these, a protein-protein interaction network was created and three significant modules critical for skeletal muscle myogenesis were found, with the most significant module A containing four recognized hub genes - EGFR, VEGFA, CDH1, and CAV1. Using the miRWALK and TF2DNA databases, miRNAs (bta-miR-2374 and bta-miR-744) and transcription factors (CEBPB, KLF15, RELA, ZNF143, ZBTB48, and REST) associated with hub genes were detected. Analysis of GO term and KEGG pathways showed that such processes are related to myogenesis and associated with module A: positive regulation of MAP kinase activity, vascular endothelial growth factor receptor, insulin-like growth factor binding, focal adhesion, and signaling pathways (PI3K-Akt, HIF-1, Rap1, Ras, MAPK).
CONCLUSIONS
The identified genes, common to the prenatal developmental period of skeletal muscle in livestock, are critical for later muscle development, including its growth by hypertrophy. They regulate valuable economic characteristics. Enhancing and breeding animals according to the recognized genes seems essential for breeders to achieve superior gains in high-quality muscle mass.
Topics: Swine; Animals; Cattle; Sheep; Gene Expression Profiling; Livestock; Proto-Oncogene Proteins c-akt; Phosphatidylinositol 3-Kinases; AMP-Activated Protein Kinases; Peroxisome Proliferator-Activated Receptors; Vascular Endothelial Growth Factor A; Muscle, Skeletal; MicroRNAs; Muscle Development
PubMed: 38504177
DOI: 10.1186/s12864-024-10196-3 -
Environmental Toxicology and... Apr 2024Exposure to organic solvents is associated with various health problems, including neurodegenerative diseases. Among these solvents, 1,2-diethylbenzene is notable for...
Exposure to organic solvents is associated with various health problems, including neurodegenerative diseases. Among these solvents, 1,2-diethylbenzene is notable for its ability to produce a toxic metabolite, 1,2-Diacetylbenzene (DAB), which can cause memory impairment. Prolactin (PRL) is theorized to protect the central nervous system. Certain antipsychotic drugs, known for increasing PRL secretion, have shown to improve cognitive performance in psychotic Alzheimer's patients. Among these, amisulpride stands out for its high efficacy, limited side effects, and high selectivity for dopamine D2 receptors. In our study, we explored the potential of amisulpride to inhibit DAB-induced neurotoxicity via PRL activation. Our results show that amisulpride enhances the PRL/JAK/STAT, PI3K/AKT, and BDNF/ERK/CREB pathways, playing critical roles in PRL's neuroprotection pathways and memory formation. Additionally, amisulpride inhibited DAB-triggered NLRP3 inflammasome activation and apoptosis. Collectively, these findings suggest that amisulpride may be a promising therapeutic intervention for DAB-induced neurotoxicity, partly through activating the PRL pathway.
Topics: Humans; Acetophenones; Amisulpride; Antipsychotic Agents; Phosphatidylinositol 3-Kinases; Prolactin; Solvents
PubMed: 38493881
DOI: 10.1016/j.etap.2024.104418