The role of kisspeptin in neuroendocrine disorders Maria

The role of kisspeptin in neuroendocrine disorders Maria Földi & Esther Hazane Leroyer JPEMS 2015, Szeged Under the supervision of Dr. Krisztina Csabafi, M. D, Ph. D, Department of Pathophysiology

Introduction Kiss 1 receptor Kisspeptin (protein) Kisspeptin gene and its protein products : kisspeptin-54, kisspeptin-13, kisspeptin-10. (http: //d 6 igaq 6 njxgjh. cloudfront. net/content/physrev/92/3/1235/F 2. large. jpg) http: //physiologyonline. physiology. org/content/nips/25/4/207/F 3. medium. gif

Localization Kiss 1 m. RNA : • Hypothalamus : • Arcuate nucleus • Anteroperiventricular nucleus • Limbic system : Amygdala M. Tena-Sempere, Handbook of biologically active peptides (2013) GPR 54 m. RNA : • Hypothalamus : Arcuate nucleus (Gn. RH neurons) • Limbic system : • Amygdala • Hippocampus

Physiology: ovarian cycle http: //d 6 igaq 6 njxgjh. cloudfront. net/conte nt/physrev/92/3/1235/F 15. large. jpg

Physiology: sexual dimorphism of the brain Male Female Less kisspeptin neurons in AVPV More kisspeptin neurons in AVPV NOT able to develop the LH surge ABLE to develop the LH surge T, E 2 : high level in the perinatal period T, E 2 : low level in the perinatal period Clarkson et al. , 2014

Pathology: Poly. Cystic Ovary Syndrome (PCOS) Kiss 1 m. RNA expression Symtomps: - Anovulation - enlarged polycistic ovaries - irregular cycle - insulin resistance One of the proposed causes: hyperandrogenism prepubertal or fetal (DHT) Kisspeptin’s role Brown et al. , 2012

Kisspeptin, Puberty & Metabolism Puberty ? • Bone age + Critical fat mass • Leptin receptors Kisspeptin Gn. RH • More and more sensitive • ↑ LH & FSH • ↑ Sex-steroids Puberty

Pathology: Precocious Puberty Development of secondary sexual characters, before the age of 7 for girls and 9 for boys. • Immature bone age • Immature critical fat mass • BUT activating mutation Kisspeptin Gn. RH • Gn. RH pulses • ↑ LH & FSH • ↑ Sex-steroids • No menarches Puberty

Pathology : Hypogonadotropic Hypogonadism. • Prevalence : 1/100000 • Congenital: 1/3 idiopathic • 2003 mutation discovered • INACTIVATING MUTATION Ø Kisspeptin Ø Gn. RH • KISS 1 R decrease of signalling pathway • ↓ LH & FSH • ↓ Sex-steroids Sexual maturation - Absence of spontaneous sexual maturation - Low blood levels of steroids

Pathology: Obesity & Diabetes. No Gn. RH • Kiss 1 r KO female MICE Ø Kisspeptin system • Glucoseresistance • ↑ Body weight • ↑ Leptin levels • ↓ LH & FSH • ↓ Sex-steroids Sexual dysfunctions • Role of kisspeptin • Sexual dimorphism Adapted from Talson et al, 2014

Potential therapeutic role: IVF h. CG • used to trigger ovulation • side-effect: OHSS Kisspeptin: Hope: more physiological and safer medication in order to elicit the ovulation: experiment (Brown et al. ) „Kisspeptin-babies”: live births after kisspeptin treatment http: //image. slidesharecdn. com/kisspeptin 2 -150516121457 -lva 1 -app 6891/95/kisspeptinhope-about-to-become-reality-13 -638. jpg? cb=1431781372

Conclusion : Kisspeptin’s role in neuroendocrine disorders. In Vitro Fertilization - Hypogonadotropic hypogonadism - Diabetes and Obesity - Precocious puberty - PCOS T h e r a p y Pat h oph ysi - Ovarian cycle - Puberty olo s gy o l io gy y Ph

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