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Kisspeptin as a test of hypothalamic dysfunction in pubertal and reproductive disorders.
Andrology
January 2025
Section of Endocrinology and Investigative Medicine, Imperial College London, London, UK.
The hypothalamic-pituitary-gonadal axis is regulated by the gonadotropin-releasing hormone pulse generator in the hypothalamus. This is comprised of neurons that secrete kisspeptin in a pulsatile manner to stimulate the release of GnRH, and, in turn, downstream gonadotropins from the pituitary gland, and subsequently sex steroids and gametogenesis from the gonads. Many reproductive disorders in both males and females are characterized by hypothalamic dysfunction, including functional disorders (such as age-related hypogonadism, obesity-related secondary hypogonadism, hyperprolactinemia, functional hypothalamic amenorrhea and polycystic ovary syndrome), structural pathologies (such as craniopharyngiomas or radiation or surgery-related hypothalamic dysfunction), and pubertal disorders (constitutional delay of growth and puberty and congenital hypogonadotropic hypogonadism).
View Article and Find Full Text PDFThe specific role that prolactin plays in lactational infertility, as distinct from other suckling or metabolic cues, remains unresolved. Here, deletion of the prolactin receptor (Prlr) from forebrain neurons or arcuate kisspeptin neurons resulted in failure to maintain normal lactation-induced suppression of estrous cycles. Kisspeptin immunoreactivity and pulsatile LH secretion were increased in these mice, even in the presence of ongoing suckling stimulation and lactation.
View Article and Find Full Text PDFKisspeptin and Neurokinin B: roles in reproductive health.
Physiol Rev
January 2025
Department of Investigative Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom.
Kisspeptin and neurokinin B (NKB) play a key role in several physiological processes including in puberty, adult reproductive function including the menstrual cycle, as well as mediating the symptoms of menopause. Infundibular kisspeptin neurons, which co-express NKB, regulate the activity of gonadotropin releasing hormone (GnRH) neurons, and thus the physiological pulsatile secretion of GnRH from the hypothalamus. Outside of their hypothalamic reproductive roles, these peptides are implicated in several physiological functions including sexual behavior and attraction, placental function, and bone health.
View Article and Find Full Text PDFKisspeptin and Endometriosis-Is There a Link?
J Clin Med
December 2024
Department of Gynecological Endocrinology, Poznan University of Medical Sciences, 60-535 Poznan, Poland.
This article presents a narrative review that explores the potential link between kisspeptin-a key regulator of the hypothalamic-pituitary-gonadal axis-and the pathogenesis of endometriosis. Kisspeptin plays a significant role in regulating reproductive functions by modulating the release of gonadotropin-releasing hormone (GnRH), which in turn stimulates the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Recent studies suggest that kisspeptin may also impact peripheral reproductive tissues and influence inflammatory processes involved in the development of endometriosis.
View Article and Find Full Text PDFDesign and implication of a breast cancer-targeted drug delivery system utilizing the Kisspeptin/GPR54 system.
Int J Pharm
January 2025
Institute of Biochemistry and Molecular Biology, School of Life Sciences, Lanzhou University, Lanzhou, Gansu 730000, China. Electronic address:
Kisspeptins function as endogenous ligands for the G protein-coupled receptor GPR54. While the primary role of the Kisspeptin/GPR54 signaling pathway pertains to reproduction, several studies have shown that GPR54 is highly expressed in breast cancer, and we further confirmed this result that GPR54 expression is significantly upregulated in breast cancer cells. Based on this finding, we developed a liposomal drug delivery system utilizing the Kisspeptin/GPR54 system to treat breast cancer after confirming the safety of Kp-10-228.
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