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      Current Insights in Prolactin Signaling and Ovulatory Function

      International Journal of Molecular Sciences
      MDPI AG

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          Abstract

          Prolactin (PRL) is a pleiotropic hormone released from lactotrophic cells of the anterior pituitary gland that also originates from extrapituitary sources and plays an important role in regulating lactation in mammals, as well as other actions. Acting in an endocrine and paracrine/autocrine manner, PRL regulates the hypothalamic–pituitary–ovarian axis, thus influencing the maturation of ovarian follicles and ovulation. This review provides a detailed discussion of the current knowledge on the role of PRL in the context of ovulation and ovulatory disorders, particularly with regard to hyperprolactinemia, which is one of the most common causes of infertility in women. Much attention has been given to the PRL structure and the PRL receptor (PRLR), as well as the diverse functions of PRLR signaling under normal and pathological conditions. The hormonal regulation of the menstrual cycle in connection with folliculogenesis and ovulation, as well as the current classifications of ovulation disorders, are also described. Finally, the state of knowledge regarding the importance of TIDA (tuberoinfundibular dopamine), KNDγ (kisspeptin/neurokinin B/dynorphin), and GnRH (gonadotropin-releasing hormone) neurons in PRL- and kisspeptin (KP)-dependent regulation of the hypothalamic–pituitary–gonadal (HPG) axis in women is reviewed. Based on this review, a rationale for influencing PRL signaling pathways in therapeutic activities accompanying ovulation disorders is presented.

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          Most cited references309

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          Fertility and infertility: Definition and epidemiology

          Infertility is a disease characterized by the failure to establish a clinical pregnancy after 12 months of regular and unprotected sexual intercourse. It is estimated to affect between 8 and 12% of reproductive-aged couples worldwide. Males are found to be solely responsible for 20-30% of infertility cases but contribute to 50% of cases overall. Secondary infertility is the most common form of female infertility around the globe, often due to reproductive tract infections. The three major factors influencing the spontaneous probability of conception are the time of unwanted non-conception, the age of the female partner and the disease-related infertility. The chance of becoming spontaneously pregnant declines with the duration before conception. The fertility decline in female already starts around 25-30 years of age and the median age at last birth is 40-41 years in most studied populations experiencing natural fertility. The disease-related infertility may affect both genders or be specific to one gender. The factors affecting both genders' fertility are hypogonadotrophic hypogonadism, hyperprolactinemia, disorders of ciliary function, cystic fibrosis, infections, systemic diseases and lifestyle related factors/diseases. Premature ovarian insufficiency, polycystic ovary syndrome, endometriosis, uterine fibroids and endometrial polyps may play a role in female infertility. Male infertility may be due to testicular and post-testicular deficiencies. Semen decline that has been observed over the years, endocrine disrupting chemicals and consanguinity are other factors that may be involved.
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            TGF-β and the TGF-β Family: Context-Dependent Roles in Cell and Tissue Physiology.

            The transforming growth factor-β (TGF-β) is the prototype of the TGF-β family of growth and differentiation factors, which is encoded by 33 genes in mammals and comprises homo- and heterodimers. This review introduces the reader to the TGF-β family with its complexity of names and biological activities. It also introduces TGF-β as the best-studied factor among the TGF-β family proteins, with its diversity of roles in the control of cell proliferation and differentiation, wound healing and immune system, and its key roles in pathology, for example, skeletal diseases, fibrosis, and cancer.
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              Cyclic decidualization of the human endometrium in reproductive health and failure.

              Decidualization denotes the transformation of endometrial stromal fibroblasts into specialized secretory decidual cells that provide a nutritive and immunoprivileged matrix essential for embryo implantation and placental development. In contrast to most mammals, decidualization of the human endometrium does not require embryo implantation. Instead, this process is driven by the postovulatory rise in progesterone levels and increasing local cAMP production. In response to falling progesterone levels, spontaneous decidualization causes menstrual shedding and cyclic regeneration of the endometrium. A growing body of evidence indicates that the shift from embryonic to maternal control of the decidual process represents a pivotal evolutionary adaptation to the challenge posed by invasive and chromosomally diverse human embryos. This concept is predicated on the ability of decidualizing stromal cells to respond to individual embryos in a manner that either promotes implantation and further development or facilitates early rejection. Furthermore, menstruation and cyclic regeneration involves stem cell recruitment and renders the endometrium intrinsically capable of adapting its decidual response to maximize reproductive success. Here we review the endocrine, paracrine, and autocrine cues that tightly govern this differentiation process. In response to activation of various signaling pathways and genome-wide chromatin remodeling, evolutionarily conserved transcriptional factors gain access to the decidua-specific regulatory circuitry. Once initiated, the decidual process is poised to transit through distinct phenotypic phases that underpin endometrial receptivity, embryo selection, and, ultimately, resolution of pregnancy. We discuss how disorders that subvert the programming, initiation, or progression of decidualization compromise reproductive health and predispose for pregnancy failure.
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                Author and article information

                Contributors
                (View ORCID Profile)
                Journal
                IJMCFK
                International Journal of Molecular Sciences
                IJMS
                MDPI AG
                1422-0067
                February 2024
                February 06 2024
                : 25
                : 4
                : 1976
                Article
                10.3390/ijms25041976
                38396659
                1379f2cd-f7b5-4ff0-a04d-3f4ff69edd7d
                © 2024

                https://creativecommons.org/licenses/by/4.0/

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