Sexual maturation and maintenance of reproductive function are regulated by neurohormonal communication between the hypothalamus, pituitary, and gonads (referred to as the HPG axis). Phoenixin (PNX) is a newly identified, endogenous peptide abundantly produced in the hypothalamus and shown to be an important mediator of ovarian cyclicity. However, the underlying mechanisms by which phoenixin functions within the HPG axis are unknown. Previous in vitro studies demonstrated a direct action of PNX on gonadotrophs to potentiate gonadotrophin-releasing hormone (GnRH) induced luteinizing hormone (LH) secretion. Therefore, we hypothesized that centrally derived phoenixin regulates the preovulatory LH surge required for ovarian cyclicity. We observed a significant dose-related increase in the level of plasma LH in diestrous, female rats that were given an intracerebroventricular injection of PNX compared with vehicle-treated controls. While this suggests that even under low-estrogen conditions, PNX acts centrally to stimulate the HPG axis, further characterization is contingent on the elucidation of its cognate receptor. Using the "deductive ligand receptor matching strategy," we identified the orphan G protein-coupled receptor, Gpr173, as our top candidate. In cultured pituitary cells, siRNA-targeted compromise of Gpr173 abrogated PNX's action to potentiate GnRH-stimulated LH secretion. In addition, siRNA-mediated knockdown of endogenous Gpr173, which localized to several hypothalamic sites related to reproductive function, not only significantly extended the estrous cycle but also prevented the PNX-induced LH secretion in diestrous, female rats. These studies are the first to demonstrate a functional relationship between PNX and Gpr173 in reproductive physiology and identify a potential therapeutic target for ovulatory dysfunction.
Objective: Research suggests that adolescents seeking gender-affirming hormone therapy experience elevated rates of depression, anxiety, and difficulties with peer relationships. Less is known regarding more specific aspects of mental health and psychosocial functioning. Furthermore, few studies have explored variations in mental health and psychosocial functioning by age, gender, degree of physical dysphoria, and informant type (adolescent, mother, and father). Method: Participants are adolescents (n = 149) and parents/guardians (n = 247) who presented to a multidisciplinary gender clinic in Dallas, TX for an initial assessment before initiation of gender-affirming hormone therapy. Adolescents completed the Youth Self-Report (YSR) and the Body Image Scale (a measure of physical dysphoria), and parents/guardians completed the Child Behavior Checklist (CBCL). Results: Approximately half of participants reported clinically significant difficulties with internalizing symptoms and psychosocial functioning (particularly engagement in activities), with approximately one-third indicating significant difficulties with depression, anxiety, obsessive compulsive, and posttraumatic stress symptoms. Parents reported fewer symptoms than adolescents across several subscales, but differences were generally small. By contrast, gender differences were found across all internalizing subscales and were generally large. Age and body dissatisfaction were not independently associated with broadband measures but, in combination with gender, were strongly associated with variance in YSR and CBCL reports of internalizing symptoms. Conclusion: Elevated rates of depression, anxiety, and competency difficulties were broadly consistent with the previous literature and demonstrate the need for investment in the clinical training and infrastructure to provide comprehensive care to this population. Differences in mental health and psychosocial functioning by gender and clinic location appear to be less straightforward.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with đź’™ for researchers
Part of the Research Solutions Family.