kiss1-protein--human and Endometriosis

Kisspeptins, encoded by the KISS1 gene, are a family of polypeptides that bind the kisspeptin receptor (KISS1R) to perform biological functions. Produced mainly in the hypothalamus, these neuropeptides regulate the pulsatile secretion of GnRH and trigger the hypothalamus-pituitary-gonadal axis. Other peripheral organs also express kisspeptin, which inhibits metastasis. Kisspeptin and KISS1R are reportedly present in the endometrium and may play roles in limiting the migration and invasion of trophoblasts into the endometrium during pregnancy (decidua) to maintain endometrial homeostasis. A deficiency of kisspeptin and KISS1R in the endometrium can lead to pathological conditions such as endometriosis and endometrial carcinoma. Kisspeptin and KISS1R in the endometrium can also promote endometrial receptivity and decidualization. Overall, kisspeptin and KISS1R are important for maintaining the normal physiological functions of the endometrium. By summarizing the roles of kisspeptin and KISS1R in the endometrium, our review explores the regulatory roles in the peripheral reproductive system of this peptide family that plays broad and profound roles in many physiological processes.

Topics: Endometriosis; Endometrium; Female; Gonadotropin-Releasing Hormone; Humans; Kisspeptins; Pregnancy; Receptors, Kisspeptin-1

Kisspeptin is now known to be an important regulator of the hypothalamic--pituitary-gonadal axis and is the target of a range of regulators, such as steroid hormone feedback, nutritional and metabolic regulation. Kisspeptin binds to its cognate receptor, KISS1R (also called GPR54), on GnRH neurons and stimulates their activity, which in turn provides an obligatory signal for GnRH secretion-thus gating down-stream events supporting reproduction. The development of peripherally active kisspeptin antagonists could offer a unique therapeutic agent for treating hormone-dependent disorders of reproduction, including precocious puberty, endometriosis, and metastatic prostate cancer. The following chapter discusses the advances made in the search for both peptide and small molecule kisspeptin antagonists and their use in delineating the role of kisspeptin within the reproductive system. To date, four peptide antagonists and one small molecule antagonist have been designed.

Topics: Animals; Endometriosis; Female; Gonadotropin-Releasing Hormone; Humans; Infertility; Kisspeptins; Male; Neurons; Prostatic Neoplasms; Puberty, Precocious; Receptors, G-Protein-Coupled; Receptors, Kisspeptin-1; Reproduction

The diagnosis of endometriosis may delay for many years due to non-deterministic symptoms and avoiding surgical interventions. Kisspeptins are hormones that interact with endometrial tissue to limit invasions during placentation and various cancers and are suggested to be also associated with endometriosis. This study evaluated if serum kisspeptin levels are associated with the invasion depth in endometriosis. Forty patients between 18 and 45 years of age and admitted to a tertiary-care Obstetrics and Gynecology Department between 2020 and 2021 with a diagnosis of endometriosis, and 40 patients without endometrioma were included in the study. Demographic, obstetric, clinical, and biochemical characteristics were evaluated in patients with superficial (SE) and deep infiltrating (DIE) endometriosis and healthy controls. Twenty patients (50%) had SE, 14 (35%) had DIE, and 22 (55%) had endometrioma in the patient group. Fertility rates were higher among controls, but similar between patients with SE and DIE. CA125 levels were significantly higher in the DIE group. SE and DIE groups had similar kisspeptin values, significantly higher than controls. CA125 and kisspeptin levels were not correlated in study groups. Serum kisspeptin levels were significantly different between endometriosis patients and healthy controls. However, kisspeptin levels were unable to differentiate endometriosis severity. Our results suggest that kisspeptins might play a role in the pathogenesis of endometriosis, which needs further assessment in more comprehensive studies.

Topics: Adolescent; Adult; CA-125 Antigen; Endometriosis; Female; Humans; Kisspeptins; Middle Aged; Ovary; Prospective Studies; Young Adult

Endometriosis is characterized by the presence of ectopic endometrial tissues. Mechanisms of tissue dissemination in endometriosis may be similar to those involved in tumor metastasis. We hypothesize that dysregulation of kisspeptin (KISS1), a metastasis suppressor in endometrial carcinoma, may contribute to the pathogenesis of endometriosis. In this study, we characterized the immunoreactivity of kisspeptin and its receptor, KISS1R, in eutopic and ectopic endometrial tissue of women with and without endometriosis, in proliferative and secretory menstrual cycle phases. Immunohistochemistry was performed using KISS1 and KISS1R antibodies on samples from women with (n = 35) and without (n = 14) endometriosis. Samples from women with endometriosis included eutopic endometrium (n = 20) samples, superficial endometriotic implants (SUP, n = 10) deep infiltrating endometriotic implants (DIE, n = 15), and ovarian endometriomas (OMA, n = 15). Immunoreactivity was quantified using histoscores. KISS1 and KISS1R immunoreactivity was significantly lower in eutopic endometrial stroma of women with versus without endometriosis, regardless of the menstrual cycle phase (P = 0.001 and P = 0.015 respectively). In endometriotic implants, KISS1 levels were significantly lower in both glandular and stromal components of DIE (P < 0.01) and OMA (P < 0.01) compared to SUP. KISS1R immunoreactivity was lower in the glandular component of OMA (P = 0.035) compared to SUP. KISS1 and KISS1R levels are lower in eutopic endometrial stroma from women with versus without endometriosis, consistent with a role for decreased KISS1 expression in the pathogenesis of endometriosis. As deeply invasive lesions showed lower KISS1 levels than superficial lesions, downregulation of KISS1 levels may contribute to implant invasiveness.

Topics: Adult; Endometriosis; Endometrium; Female; Humans; Immunohistochemistry; Kisspeptins; Middle Aged; Ovarian Diseases; Receptors, Kisspeptin-1

To analyze the expression pattern of metastasis suppressors KAI1 and KISS1 in the endometrium of patients with and without endometriosis.. In this pilot study, tissue samples were prospectively collected from 38 patients with endometriosis and 29 without endometriosis, undergoing operative laparoscopy in the proliferative phase of the menstrual cycle; diagnosis or absence of endometriosis was confirmed histologically. Protein expression of KAI1 and KISS1 were analyzed immunohistochemically in endometriotic lesions and the eutopic endometrium of patients with endometriosis and without endometriosis.. KAI1 expression was significantly decreased in the glandular eutopic endometrium of endometriosis patients as compared with that of patients without endometriosis (p=0.008). On the other hand, in endometriosis patients, KAI1 expression was significantly increased in the ectopic as compared with the eutopic endometrial stroma (p=0.021). There were no other significant differences in KAI1 expression between different groups. KISS1 expression in the ectopic glandular endometrium was significantly increased as compared with the eutopic glandular endometrium from patients with (p=0.004) and without endometriosis (p=0.008). There was no significant difference in KISS1 protein expression in the stromal endometrium between the three groups.. KAI1 and KISS1 are implicated in the pathogenesis and maintenance of endometriosis. Future studies should investigate whether KAI1 and KISS1 could be used as markers for early and minimally invasive detection of endometriosis based on their differential protein expression pattern in the eutopic endometrium of patients with and without endometriosis.

Topics: Adult; Endometriosis; Endometrium; Female; Humans; Immunohistochemistry; Kangai-1 Protein; Kisspeptins; Pilot Projects; Prospective Studies