Title: Is Oxytocin "Nature's Medicine"?
In: Pharmacological Reviews 2020 Oct;72(4):829-861. doi: 10.1124/pr.120.019398.
Authors: C Sue Carter, William M Kenkel, Evan L MacLean, Steven R Wilson, Allison M Perkeybile, Jason R Yee, Craig F Ferris, Hossein P Nazarloo, Stephen W Porges, John M Davis, Jessica J Connelly, Marcy A Kingsbury.
Abstract: “Oxytocin is a pleiotropic, peptide hormone with broad implications for general health, adaptation, development, reproduction, and social behavior. Endogenous oxytocin and stimulation of the oxytocin receptor support patterns of growth, resilience, and healing. Oxytocin can function as a stress-coping molecule, an anti-inflammatory, and an antioxidant, with protective effects especially in the face of adversity or trauma. Oxytocin influences the autonomic nervous system and the immune system. These properties of oxytocin may help explain the benefits of positive social experiences and have drawn attention to this molecule as a possible therapeutic in a host of disorders. However, as detailed here, the unique chemical properties of oxytocin, including active disulfide bonds, and its capacity to shift chemical forms and bind to other molecules make this molecule difficult to work with and to measure. The effects of oxytocin also are context-dependent, sexually dimorphic, and altered by experience. In part, this is because many of the actions of oxytocin rely on its capacity to interact with the more ancient peptide molecule, vasopressin, and the vasopressin receptors. In addition, oxytocin receptor(s) are epigenetically tuned by experience, especially in early life. Stimulation of G-protein-coupled receptors triggers subcellular cascades allowing these neuropeptides to have multiple functions. The adaptive properties of oxytocin make this ancient molecule of special importance to human evolution as well as modern medicine and health; these same characteristics also present challenges to the use of oxytocin-like molecules as drugs that are only now being recognized. SIGNIFICANCE STATEMENT: Oxytocin is an ancient molecule with a major role in mammalian behavior and health. Although oxytocin has the capacity to act as a "natural medicine" protecting against stress and illness, the unique characteristics of the oxytocin molecule and its receptors and its relationship to a related hormone, vasopressin, have created challenges for its use as a therapeutic drug.”
Open access: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7495339/
Title: An Emerging Role for Prolactin in Female-Selective Pain.
In: Trends in Neuroscience 2020 Aug;43(8):635-648. doi: 10.1016/j.tins.2020.06.003.
Authors: Yanxia Chen, Edita Navratilova, David W. Dodick, Frank Porreca.
“Highlights: Women display a higher prevalence of many pain conditions, suggesting a role for sexually dimorphic pain mechanisms. Emerging evidence implicates the prolactin (PRL) and prolactin receptor (PRLR) system as a female-selective mechanism promoting pain in females. PRL signals differentially through long and short PRLR (PRLR-L and PRLR-S) that reciprocally inhibit PRL signaling. Increased nociceptor excitability and pain result from PRL signaling through PRLR-S. Dysregulation of PRLR isoforms in pathological states may provide a basis for female-prevalent pain disorders, and allow the development of therapeutic strategies for improved treatment of pain in women.”
Abstract: “Women experience many pain conditions more frequently when compared with men, but the biological mechanisms underlying sex differences in pain remain poorly understood. In particular, little is known about possible sex differences in peripheral nociceptors, the fundamental building blocks of pain transmission. Emerging evidence reveals that prolactin (PRL) signaling at its cognate prolactin receptor (PRLR) in primary afferents promotes nociceptor sensitization and pain in a female-selective fashion. In this review, we summarize recent progress in understanding the female-selective role of PRL/PRLR in nociceptor sensitization and in pathological pain conditions, including postoperative, inflammatory, neuropathic, and migraine pain, as well as opioid-induced hyperalgesia. The clinical implications of the peripheral PRL/PRLR system for the discovery of new therapies for pain control in women are also discussed.”
Abstract: DOI:https://doi.org/10.1016/j.tins.2020.06.003
Title: Prolactin: A hormone with diverse functions from mammary gland development to cancer metastasis.
In: Seminars in Cell & Developmental Biology 2020 Oct 24;S1084-9521(20)30164-6.
Authors: Ödül Karayazi Atıcı PhD, Nayantara Govindrajan, Isbel Lopetegui-González, Carrie S.Shemanko.
Abstract: “Prolactin has a rich mechanistic set of actions and signaling in order to elicit developmental effects in mammals. Historically, prolactin has been appreciated as an endocrine peptide hormone that is responsible for final, functional mammary gland development and lactation. Multiple signaling pathways impacted upon by the microenvironment contribute to cell function and differentiation. Endocrine, autocrine and paracrine signaling are now apparent in not only mammary development, but also in cancer, and involve multiple cell types including those of the immune system. Multiple ligands agonists are capable of binding to the prolactin receptor, potentially expanding receptor function. Prolactin has an important role not only in tumorigenesis of the breast, but also in a number of hormonally responsive cancers such as prostate, ovarian and endometrial cancer, as well as pancreatic and lung cancer. Although pituitary and extra-pituitary sources of prolactin such as the epithelium are important, stromal sourced prolactin is now also being recognized as an important factor in tumor progression, all of which potentially signal to multiple cell types in the tumor microenvironment. While prolactin has important roles in milk production including calcium and bone homeostasis, in the disease state it can also affect bone homeostasis. Prolactin also impacts metastatic cancer of the breast to modulate the bone microenvironment and promote bone damage. Prolactin has a fascinating contribution in both physiologic and pathologic settings of mammals.”
Abstract: https://www.sciencedirect.com/science/article/abs/pii/S1084952120301646?via%3Dihub