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Journal of Experimental Zoology. Part... Dec 2022In most animals, annual rhythms in environmental cues and internal programs regulate seasonal physiology and behavior. Prolactin, an evolutionarily ancient hormone,... (Review)
Review
In most animals, annual rhythms in environmental cues and internal programs regulate seasonal physiology and behavior. Prolactin, an evolutionarily ancient hormone, serves as a molecular correlate of seasonal timing in most species. Prolactin is highly pleiotropic with a wide variety of well-documented physiological effects; in a seasonal context prolactin is known to regulate annual changes in pelage and molt. While short-term homeostatic variation of prolactin secretion is under the control of the hypothalamus, long-term seasonal rhythms of prolactin are programmed by endogenous timers that reside in the pituitary gland. The molecular basis of these rhythms is generally understood to be melatonin dependent in mammals. Prolactin rhythmicity persists for several years in many species, in the absence of hypothalamic signaling. Such evidence in mammals has supported the hypothesis that seasonal rhythms in prolactin derive from an endogenous timer within the pituitary gland that is entrained by external photoperiod. In this review, we describe the conserved nature of prolactin signaling in birds and mammals and highlight its role in regulating multiple diverse physiological systems. The review will cover the current understanding of the molecular control of prolactin seasonality and propose a mechanism by which long-term rhythms may be generated in amniotes.
Topics: Animals; Prolactin; Seasons; Photoperiod; Birds; Mammals
PubMed: 35686456
DOI: 10.1002/jez.2634 -
Frontiers in Endocrinology 2023
Topics: Humans; Female; Hyperprolactinemia; Prolactin; Polycystic Ovary Syndrome
PubMed: 38274234
DOI: 10.3389/fendo.2023.1351471 -
Frontiers in Endocrinology 2022Prolactin coordinates with the ovarian steroids to orchestrate mammary development and lactation, culminating in nourishment and an increasingly appreciated array of... (Review)
Review
Prolactin coordinates with the ovarian steroids to orchestrate mammary development and lactation, culminating in nourishment and an increasingly appreciated array of other benefits for neonates. Its central activities in mammary epithelial growth and differentiation suggest that it plays a role(s) in breast cancer, but it has been challenging to identify its contributions, essential for incorporation into prevention and treatment approaches. Large prospective epidemiologic studies have linked higher prolactin exposure to increased risk, particularly for ER+ breast cancer in postmenopausal women. However, it has been more difficult to determine its actions and clinical consequences in established tumors. Here we review experimental data implicating multiple mechanisms by which prolactin may increase the risk of breast cancer. We then consider the evidence for role(s) of prolactin and its downstream signaling cascades in disease progression and treatment responses, and discuss how new approaches are beginning to illuminate the biology behind the seemingly conflicting epidemiologic and experimental studies of prolactin actions across diverse breast cancers.
Topics: Breast Neoplasms; Disease Progression; Female; Humans; Infant, Newborn; Lactation; Prolactin; Prospective Studies
PubMed: 35784527
DOI: 10.3389/fendo.2022.910978 -
Pituitary Feb 2020Prolactinomas are the most frequently seen pituitary adenomas in clinical practice. A correct biochemical diagnosis of hyperprolactinemia is a prerequisite for further... (Review)
Review
Prolactinomas are the most frequently seen pituitary adenomas in clinical practice. A correct biochemical diagnosis of hyperprolactinemia is a prerequisite for further investigation but may be hampered by analytical difficulties as well as a large number of potentially overlapping conditions associated with increased prolactin levels. Suspicion should rise in patients whose symptoms and biochemical results do not match. Assay problems, macroprolactinemia, and high-dose hook effect are discussed as possible reasons for false positive or false negative prolactin levels. Physiological and pathological causes of hyperprolactinemia and their implications for interpreting prolactin results are reviewed.
Topics: Humans; Hyperprolactinemia; Prolactin; Prolactinoma
PubMed: 31873848
DOI: 10.1007/s11102-019-01024-z -
Nature Reviews. Endocrinology Dec 2023Traditional textbook physiology has ascribed unitary functions to hormones from the anterior and posterior pituitary gland, mainly in the regulation of effector hormone... (Review)
Review
Traditional textbook physiology has ascribed unitary functions to hormones from the anterior and posterior pituitary gland, mainly in the regulation of effector hormone secretion from endocrine organs. However, the evolutionary biology of pituitary hormones and their receptors provides evidence for a broad range of functions in vertebrate physiology. Over the past decade, we and others have discovered that thyroid-stimulating hormone, follicle-stimulating hormone, adrenocorticotropic hormone, prolactin, oxytocin and arginine vasopressin act directly on somatic organs, including bone, adipose tissue and liver. New evidence also indicates that pituitary hormone receptors are expressed in brain regions, nuclei and subnuclei. These studies have prompted us to attribute the pathophysiology of certain human diseases, including osteoporosis, obesity and neurodegeneration, at least in part, to changes in pituitary hormone levels. This new information has identified actionable therapeutic targets for drug discovery.
Topics: Humans; Pituitary Hormones; Pituitary Gland; Prolactin; Adipose Tissue; Brain
PubMed: 37715028
DOI: 10.1038/s41574-023-00894-5 -
Frontiers in Endocrinology 2022The role of prolactin (PRL) favoring metabolic homeostasis is supported by multiple preclinical and clinical studies. PRL levels are key to explaining the direction of... (Review)
Review
The role of prolactin (PRL) favoring metabolic homeostasis is supported by multiple preclinical and clinical studies. PRL levels are key to explaining the direction of its actions. In contrast with the negative outcomes associated with very high (>100 μg/L) and very low (<7 μg/L) PRL levels, moderately high PRL levels, both within but also above the classically considered physiological range are beneficial for metabolism and have been defined as HomeoFIT-PRL. In animal models, HomeoFIT-PRL levels counteract insulin resistance, glucose intolerance, adipose tissue hypertrophy and fatty liver; and in humans associate with reduced prevalence of insulin resistance, fatty liver, glucose intolerance, metabolic syndrome, reduced adipocyte hypertrophy, and protection from type 2 diabetes development. The beneficial actions of PRL can be explained by its positive effects on main metabolic organs including the pancreas, liver, adipose tissue, and hypothalamus. Here, we briefly review work supporting PRL as a promoter of metabolic homeostasis in rodents and humans, the PRL levels associated with metabolic protection, and the proposed mechanisms involved. Finally, we discuss the possibility of using drugs elevating PRL for the treatment of metabolic diseases.
Topics: Animals; Diabetes Mellitus, Type 2; Fatty Liver; Glucose Intolerance; Humans; Hypertrophy; Insulin Resistance; Prolactin
PubMed: 36213259
DOI: 10.3389/fendo.2022.1001703 -
Trends in Endocrinology and Metabolism:... Jun 2022Proteolysis of protein hormones is primarily acknowledged in the context of breakdown and metabolic clearance by hepatorenal elimination. However, less explored is the... (Review)
Review
Proteolysis of protein hormones is primarily acknowledged in the context of breakdown and metabolic clearance by hepatorenal elimination. However, less explored is the specific proteolytic processing of large protein hormones, for which canonical signaling pathways were already established [e.g., prolactin (PRL)], to generate unique messengers that impact cellular functions via pathways unrelated to the receptors of their precursor molecules. Yet, the proteolysis of PRL to generate new messengers evolved under positive selection, and cleaved protein hormones regulate essential functions to maintain homeostasis at the organismal, tissue, or organ levels. The cleavage sites at which proteolysis occurs and the proteases with their determinants define a hormone-metabolism junction at which specific proteolytic cleavage, pathological alteration, and hepatorenal elimination occur.
Topics: Hormones; Humans; Kinetics; Prolactin; Proteolysis; Signal Transduction
PubMed: 35397984
DOI: 10.1016/j.tem.2022.03.004 -
ELife Apr 2024Prolactin suppresses the ovarian cycles of lactating mice by directly repressing the activity of a cell population known as kisspeptin neurons.
Prolactin suppresses the ovarian cycles of lactating mice by directly repressing the activity of a cell population known as kisspeptin neurons.
Topics: Female; Mice; Animals; Gonadotropin-Releasing Hormone; Lactation; Fertility; Prolactin; Neurons; Kisspeptins
PubMed: 38591514
DOI: 10.7554/eLife.97432 -
Otolaryngologic Clinics of North America Apr 2022Prolactinomas are the most common secretory tumor of the pituitary gland. Clinical symptoms may be due to prolactin oversecretion, localized mass effect, or a... (Review)
Review
Prolactinomas are the most common secretory tumor of the pituitary gland. Clinical symptoms may be due to prolactin oversecretion, localized mass effect, or a combination of both. Although the mainstay of prolactinoma management is medical therapy with dopamine agonists, endoscopic endonasal or transcranial surgery, radiation therapy, or a combination of these is an important treatment option in select cases. This article discusses prolactinoma phenotypes, clinical presentations, and clinically pertinent medical and surgical considerations when managing these tumors.
Topics: Dopamine Agonists; Humans; Nose; Pituitary Neoplasms; Prolactin; Prolactinoma
PubMed: 35256169
DOI: 10.1016/j.otc.2021.12.005 -
The Journal of Headache and Pain Mar 2023Migraine is a severe neurovascular disorder of which the pathophysiology is not yet fully understood. Besides the role of inflammatory mediators that interact with the... (Review)
Review
Migraine is a severe neurovascular disorder of which the pathophysiology is not yet fully understood. Besides the role of inflammatory mediators that interact with the trigeminovascular system, cyclic fluctuations in sex steroid hormones are involved in the sex dimorphism of migraine attacks. In addition, the pituitary-derived hormone prolactin and the hypothalamic neuropeptide oxytocin have been reported to play a modulating role in migraine and contribute to its sex-dependent differences. The current narrative review explores the relationship between these two hormones and the pathophysiology of migraine. We describe the physiological role of prolactin and oxytocin, its relationship to migraine and pain, and potential therapies targeting these hormones or their receptors.In summary, oxytocin and prolactin are involved in nociception in opposite ways. Both operate at peripheral and central levels, however, prolactin has a pronociceptive effect, while oxytocin appears to have an antinociceptive effect. Therefore, migraine treatment targeting prolactin should aim to block its effects using prolactin receptor antagonists or monoclonal antibodies specifically acting at migraine-pain related structures. This action should be local in order to avoid a decrease in prolactin levels throughout the body and associated adverse effects. In contrast, treatment targeting oxytocin should enhance its signalling and antinociceptive effects, for example using intranasal administration of oxytocin, or possibly other oxytocin receptor agonists. Interestingly, the prolactin receptor and oxytocin receptor are co-localized with estrogen receptors as well as calcitonin gene-related peptide and its receptor, providing a positive perspective on the possibilities for an adequate pharmacological treatment of these nociceptive pathways. Nevertheless, many questions remain to be answered. More particularly, there is insufficient data on the role of sex hormones in men and the correct dosing according to sex differences, hormonal changes and comorbidities. The above remains a major challenge for future development.
Topics: Female; Humans; Male; Analgesics; Gonadal Steroid Hormones; Migraine Disorders; Oxytocin; Pain; Prolactin; Receptors, Oxytocin; Receptors, Prolactin
PubMed: 36967387
DOI: 10.1186/s10194-023-01557-6