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Nature Reviews. Endocrinology Jan 2023Lactation is critical to infant short-term and long-term health and protects mothers from breast cancer, ovarian cancer and type 2 diabetes mellitus. The mammary gland... (Review)
Review
Lactation is critical to infant short-term and long-term health and protects mothers from breast cancer, ovarian cancer and type 2 diabetes mellitus. The mammary gland is a dynamic organ, regulated by the coordinated actions of reproductive and metabolic hormones. These hormones promote gland development from puberty onwards and induce the formation of a branched, epithelial, milk-secreting organ by the end of pregnancy. Progesterone withdrawal following placental delivery initiates lactation, which is maintained by increased pituitary secretion of prolactin and oxytocin, and stimulated by infant suckling. After weaning, local cytokine production and decreased prolactin secretion trigger large-scale mammary cell loss, leading to gland involution. Here, we review advances in the molecular endocrinology of mammary gland development and milk synthesis. We discuss the hormonal functions of the mammary gland, including parathyroid hormone-related peptide secretion that stimulates maternal calcium mobilization for milk synthesis. We also consider the hormonal composition of human milk and its associated effects on infant health and development. Finally, we highlight endocrine and metabolic diseases that cause lactation insufficiency, for example, monogenic disorders of prolactin and prolactin receptor mutations, maternal obesity and diabetes mellitus, interventions during labour and delivery, and exposure to endocrine-disrupting chemicals such as polyfluoroalkyl substances in consumer products and other oestrogenic compounds.
Topics: Female; Humans; Pregnancy; Mammary Glands, Human; Oxytocin; Placenta; Prolactin; Lactation
PubMed: 36192506
DOI: 10.1038/s41574-022-00742-y -
Handbook of Clinical Neurology 2020The hormonal fluctuations in pregnancy drive a wide range of adaptive changes in the maternal brain. These range from specific neurophysiological changes in the patterns... (Review)
Review
The hormonal fluctuations in pregnancy drive a wide range of adaptive changes in the maternal brain. These range from specific neurophysiological changes in the patterns of activity of individual neuronal populations, through to complete modification of circuit characteristics leading to fundamental changes in behavior. From a neurologic perspective, the key hormone changes are those of the sex steroids, estradiol and progesterone, secreted first from the ovary and then from the placenta, the adrenal glucocorticoid cortisol, as well as the anterior pituitary peptide hormone prolactin and its pregnancy-specific homolog placental lactogen. All of these hormones are markedly elevated during pregnancy and cross the blood-brain barrier to exert actions on neuronal populations through receptors expressed in specific regions. Many of the hormone-induced changes are in autonomic or homeostatic systems. For example, patterns of oxytocin and prolactin secretion are dramatically altered to support novel physiological functions. Appetite is increased and feedback responses to metabolic hormones such as leptin and insulin are suppressed to promote a positive energy balance. Fundamental physiological systems such as glucose homeostasis and thermoregulation are modified to optimize conditions for fetal development. In addition to these largely autonomic changes, there are also changes in mood, behavior, and higher processes such as cognition. This chapter summarizes the hormonal changes associated with pregnancy and reviews how these changes impact on brain function, drawing on examples from animal research, as well as available information about human pregnancy.
Topics: Animals; Cognition; Female; Humans; Insulin; Leptin; Placenta; Pregnancy; Prolactin
PubMed: 32736755
DOI: 10.1016/B978-0-444-64239-4.00002-3 -
International Journal of Molecular... Jul 2020The hair cycle and hair follicle structure are highly affected by various hormones. Androgens-such as testosterone (T); dihydrotestosterone (DHT); and their prohormones,... (Review)
Review
The hair cycle and hair follicle structure are highly affected by various hormones. Androgens-such as testosterone (T); dihydrotestosterone (DHT); and their prohormones, dehydroepiandrosterone sulfate (DHEAS) and androstendione (A)-are the key factors in terminal hair growth. They act on sex-specific areas of the body, converting small, straight, fair vellus hairs into larger darker terminal hairs. They bind to intracellular androgen receptors in the dermal papilla cells of the hair follicle. The majority of hair follicles also require the intracellular enzyme 5-alpha reductase to convert testosterone into DHT. Apart from androgens, the role of other hormones is also currently being researched-e.g., estradiol can significantly alter the hair follicle growth and cycle by binding to estrogen receptors and influencing aromatase activity, which is responsible for converting androgen into estrogen (E2). Progesterone, at the level of the hair follicle, decreases the conversion of testosterone into DHT. The influence of prolactin (PRL) on hair growth has also been intensively investigated, and PRL and PRL receptors were detected in human scalp skin. Our review includes results from many analyses and provides a comprehensive up-to-date understanding of the subject of the effects of hormonal changes on the hair follicle.
Topics: Androgens; Estradiol; Female; Hair Follicle; Humans; Male; Prolactin; Sex Characteristics
PubMed: 32731328
DOI: 10.3390/ijms21155342 -
American Journal of Health-system... May 2021This article aims to evaluate management options for antipsychotic-induced hyperprolactinemia and associated treatment considerations such as efficacy, tolerability,...
PURPOSE
This article aims to evaluate management options for antipsychotic-induced hyperprolactinemia and associated treatment considerations such as efficacy, tolerability, drug interactions, contraindications, and dosing regimens.
SUMMARY
Hyperprolactinemia is a common adverse effect of antipsychotics. First-line management includes reducing the dose of the offending antipsychotic, discontinuing the antipsychotic, or switching to another antipsychotic associated with a lower risk of hyperprolactinemia. However, these options are not always practical and are associated with a risk of relapse of the psychiatric illness. Other management options include adjunctive aripiprazole, dopamine agonists (cabergoline and bromocriptine), metformin, and herbal supplements. A search of Embase, PubMed, and Google Scholar using key terms such as hyperprolactinemia, prolactin, antipsychotic, treatment guidelines, aripiprazole, dopamine agonist, cabergoline, bromocriptine, metformin, herbals, supplements, and medications was conducted for literature retrieval. Upon evaluation of the available literature we found the following: (1) aripiprazole is safe and effective in lowering prolactin levels within normal limits; (2) adjunctive cabergoline and bromocriptine decrease elevated prolactin levels, while cabergoline may be more effective in reducing prolactin but can also be associated with a more serious adverse effect of cardiac valvular abnormalities; (3) metformin causes a mild reduction of prolactin levels; and (4) there are limited data to support use of herbal medications (chamomile, Peony-Glycyrrhiza decoction, and shakuyaku-kanzo-to) in antipsychotic-induced hyperprolactinemia.
CONCLUSION
There are treatments available for antipsychotic-induced hyperprolactinemia in patients who are unable to alter their current antipsychotic regimen. However, there remains a need for additional short- and long-term studies to determine the efficacy and safety of these treatment strategies, given that patients taking antipsychotics typically require chronic, life-long treatment for their illnesses.
Topics: Antipsychotic Agents; Aripiprazole; Humans; Hyperprolactinemia; Mental Disorders; Prolactin
PubMed: 33954421
DOI: 10.1093/ajhp/zxab065 -
The Lancet. Psychiatry Oct 2021Breast cancer is more common in female patients with schizophrenia than in the general population. It is not known whether treatment with prolactin-increasing...
BACKGROUND
Breast cancer is more common in female patients with schizophrenia than in the general population. It is not known whether treatment with prolactin-increasing antipsychotics contributes to increased odds of breast cancer.
METHODS
We used Finnish nationwide registers of hospital treatment, prescription drug purchases, and cancer diagnoses to do a nested case-control study. Of women with schizophrenia, those with breast cancer (cases) were matched by age and duration of illness with five women without cancer (controls). Cases and controls were aged 18-85 years and exclusion criteria were any previous cancer diagnoses, receipt of organ transplant, mastectomy, or diagnosis of HIV. The main analysis was the association between cumulative exposure to prolactin-increasing drugs and breast cancer. The analyses were done with conditional logistic regression, by adjusting for comorbid conditions and concomitant medications. Ethnicity data were not available.
FINDINGS
Of 30 785 women diagnosed with schizophrenia between 1972 and 2014, 1069 were diagnosed with breast cancer between Jan 1, 2000, and Dec 31, 2017. Compared with 5339 matched controls, 1-4 years cumulative exposure (adjusted odds ratio [OR] 0·95, 95% CI 0·73-1·25) or 5 or more years exposure (adjusted OR 1·19, 0·90-1·58) to prolactin-sparing antipsychotics (including clozapine, quetiapine, or aripiprazole) was not associated with an increased risk of breast cancer in comparison with minimal exposure (<1 year). When compared with less than 1 year of exposure to prolactin-increasing antipsychotics (all other antipsychotics), 1-4 years of exposure was not associated with an increased risk, but exposure for 5 or more years was associated with an increased risk (adjusted OR 1·56 [1·27-1·92], p<0·001). The risk for developing lobular adenocarcinoma associated with long-term use of prolactin-increasing antipsychotics (adjusted OR 2·36 [95% CI 1·46-3·82]) was higher than that of developing ductal adenocarcinoma (adjusted OR 1·42 [95% CI 1·12-1·80]).
INTERPRETATION
Long-term exposure to prolactin-increasing, but not to prolactin-sparing, antipsychotics is significantly associated with increased odds of breast cancer. Monitoring prolactinemia and addressing hyperprolactinemia is paramount in women with schizophrenia being treated with prolactin-increasing antipsychotics.
FUNDING
Finnish Ministry of Social Affairs and Health.
Topics: Adult; Aged; Antipsychotic Agents; Breast Neoplasms; Carcinoma, Lobular; Case-Control Studies; Clozapine; Female; Finland; Humans; Middle Aged; Prolactin; Quetiapine Fumarate; Schizophrenia
PubMed: 34474013
DOI: 10.1016/S2215-0366(21)00241-8 -
Journal of Neuroendocrinology Nov 2020
Topics: Animals; Growth Hormone; Human Growth Hormone; Humans; Mice; Prolactin
PubMed: 33128814
DOI: 10.1111/jne.12909 -
Hormones (Athens, Greece) Jun 2022Prolactin, a pituitary hormone that was discovered about 80 years ago and is primarily known for its functions in mammary gland development and lactation, is now known... (Review)
Review
Prolactin, a pituitary hormone that was discovered about 80 years ago and is primarily known for its functions in mammary gland development and lactation, is now known to participate in numerous functions across different phylogenetic groups. Fundamentally known for its secretion from lactotroph cells in adenohypophysis region of pituitary gland, newer studies have demonstrated a number of extrapituitary sites which secrete prolactin, where it acts in an autocrine, paracrine, and endocrine manner to regulate essential physiological and biochemical processes. These sites include lymphocytes, epithelial cells of lactating mammary glands, breast cancer cells of epithelial origin, and the placenta. The placenta is one of the most important organs secreting prolactin; however, its role in placental biology has not to date been reviewed comprehensively. This review elaborates upon the various facets of prolactin hormone, including prolactin production and its post-translational modifications and signaling. Major emphasis is placed on placental prolactin and its potential roles, ranging from the role of prolactin in angiogenesis, preeclampsia, maternal diabetes, and anti-apoptosis, among others.
Topics: Female; Humans; Lactation; Pituitary Gland; Placenta; Pregnancy; Prolactin; Signal Transduction
PubMed: 35545690
DOI: 10.1007/s42000-022-00373-y -
The Journal of Headache and Pain Apr 2024Sexual dimorphism has been revealed for many neurological disorders including chronic pain. Prelicinal studies and post-mortem analyses from male and female human donors... (Review)
Review
Sexual dimorphism has been revealed for many neurological disorders including chronic pain. Prelicinal studies and post-mortem analyses from male and female human donors reveal sexual dimorphism of nociceptors at transcript, protein and functional levels suggesting different mechanisms that may promote pain in men and women. Migraine is a common female-prevalent neurological disorder that is characterized by painful and debilitating headache. Prolactin is a neurohormone that circulates at higher levels in females and that has been implicated clinically in migraine. Prolactin sensitizes sensory neurons from female mice, non-human primates and humans revealing a female-selective pain mechanism that is conserved evolutionarily and likely translationally relevant. Prolactin produces female-selective migraine-like pain behaviors in rodents and enhances the release of calcitonin gene-related peptide (CGRP), a neurotransmitter that is causal in promoting migraine in many patients. CGRP, like prolactin, produces female-selective migraine-like pain behaviors. Consistent with these observations, publicly available clinical data indicate that small molecule CGRP-receptor antagonists are preferentially effective in treatment of acute migraine therapy in women. Collectively, these observations support the conclusion of qualitative sex differences promoting migraine pain providing the opportunity to tailor therapies based on patient sex for improved outcomes. Additionally, patient sex should be considered in design of clinical trials for migraine as well as for pain and reassessment of past trials may be warranted.
Topics: Migraine Disorders; Humans; Female; Animals; Sex Characteristics; Calcitonin Gene-Related Peptide; Prolactin; Male
PubMed: 38658853
DOI: 10.1186/s10194-024-01771-w -
Pituitary Jun 2020Prolactin (PRL) has direct and indirect effects on bone metabolism. Experimental studies showed that in the presence of high PRL levels bone resorption was increased as... (Review)
Review
Prolactin (PRL) has direct and indirect effects on bone metabolism. Experimental studies showed that in the presence of high PRL levels bone resorption was increased as well as bone formation was suppressed. Increased PRL levels in humans caused a reduction in sex hormone levels which turn may have detrimental effects on bone. Patients with hyperprolactinemia did have often decreased bone mineral density as well as an increased risk of fractures. Since PRL control may be relevant to bone health it is a clinical open issue the inclusion of skeletal health in future guidelines as indication to proactive screening, prevention and treatment particularly in high risk patients such as hyperprolactinemic women after menopause and patients with drug induced hyperprolactinemia.
Topics: Antipsychotic Agents; Bone Density; Humans; Hyperprolactinemia; Osteoporosis; Prolactin
PubMed: 32219718
DOI: 10.1007/s11102-020-01041-3 -
Molecular and Cellular Endocrinology Feb 2020Prolactin is pleotropic in nature affecting multiple tissues throughout the body. As a consequence of the broad range of functions, regulation of anterior pituitary... (Review)
Review
Prolactin is pleotropic in nature affecting multiple tissues throughout the body. As a consequence of the broad range of functions, regulation of anterior pituitary prolactin secretion is complex and atypical as compared to other pituitary hormones. Many studies have provided insight into the complex hypothalamic-pituitary networks controlling prolactin secretion patterns in different species using a range of techniques. Here, we review prolactin secretion in both males and females; and consider the different patterns of prolactin secretion across the reproductive cycle in representative female mammals with short versus long luteal phases and in seasonal breeders. Additionally, we highlight changes in the pattern of secretion during pregnancy and lactation, and discuss the wide range of adaptive functions that prolactin may have in these important physiological states.
Topics: Animals; Female; Humans; Lactation; Luteal Phase; Male; Pregnancy; Prolactin
PubMed: 31843563
DOI: 10.1016/j.mce.2019.110679