the role of kisspeptin in neuroendocrine disorders
DESCRIPTION
Introduction Kiss1 receptor Kisspeptin (protein) http://physiologyonline.physiology.org/content/nips/25/4/207/F3.medium.gif Kiss1 receptor Kisspeptin gene and its protein products : kisspeptin-54, kisspeptin-14, kisspeptin-13, kisspeptin-10. (http://d6igaq6njxgjh.cloudfront.net/content/physrev/92/3/1235/F2.large.jpg) Kisspeptin (protein) All share the same C-ter + N-ter. RF-amide involved in nociceptive transduction, feeding behaviour, regulation of pituitary hormones secretion…TRANSCRIPT
The role of kisspeptin in neuroendocrine disorders
Maria Fldi & Esther Hazane Leroyer JPEMS 2015, Szeged Under the
supervision of Dr. Krisztina Csabafi, M.D, PhD, Department of
Pathophysiology Introduction Kiss1 receptor Kisspeptin
(protein)
Kiss1 receptor Kisspeptin gene and its protein products :
kisspeptin-54, kisspeptin-14, kisspeptin-13,
kisspeptin-10.(http://d6igaq6njxgjh.cloudfront.net/content/physrev/92/3/1235/F2.large.jpg)
Kisspeptin (protein) All share the same C-ter + N-ter. RF-amide
involved in nociceptive transduction, feeding behaviour, regulation
of pituitary hormones secretion Localization GPR54 mRNA : Kiss1
mRNA :
M. Tena-Sempere, Handbook of biologically active peptides (2013)
Kiss1 mRNA : Hypothalamus : Arcuate nucleus Anteroperiventricular
nucleus Limbic system : Amygdala GPR54 mRNA : Hypothalamus :
Arcuate nucleus (GnRH neurons) Limbic system : Amygdala Hippocampus
In the periphery, KISS1 mRNA is located at high levels in the
placenta, but in the CNS it can be mostly found in the
hypothalamus, and in the limbic system the amygdla Physiology:
ovarian cycle
Physiology: sexual dimorphism of the brain
Male Less kisspeptin neurons in AVPV NOT able to develop the LH
surge T, E2 : high level in the perinatal period Female More
kisspeptin neurons in AVPV ABLE to develop the LH surge T, E2 : low
level in the perinatal period Clarkson et al., 2014 Pathology:
PolyCystic Ovary Syndrome (PCOS)
Kiss1 mRNA expression Brown et al., 2012 Pathology: PolyCystic
Ovary Syndrome (PCOS) Symtomps: Anovulation enlarged polycistic
ovaries irregular cycle insulin resistance One of the proposed
causes: hyperandrogenism prepubertal or fetal (DHT) Kisspeptins
role Kisspeptin, Puberty & Metabolism Kisspeptin GnRH
Puberty
Bone age + Critical fat mass Leptin receptors Kisspeptin More and
more sensitive GnRH LH & FSH Sex-steroids Puberty Puberty ?
Puberty : activation of the previously dormant neuroendocrine
reproductive axis (apparition of GnRH pulses) + reaching bone age +
critical fat mass. Pathology: Precocious Puberty
Development of secondarysexual characters, before theage of 7 for
girls and 9 forboys. Immature bone age Immature critical fat mass
BUT activating mutation Kisspeptin GnRH pulses GnRH LH & FSH
Sex-steroids No menarches Puberty Pathology : Hypogonadotropic
Hypogonadism.
INACTIVATING MUTATION Kisspeptin KISS1R decrease of signalling
pathway GnRH LH & FSH Sex-steroids Sexual maturation Prevalence
: 1/100000 Congenital: 1/3 idiopathic 2003 mutation discovered 1/ :
congenital or acquired Idiopathic HH (1/3) Absence of spontaneous
sexual maturation + low blood levels of steroids (absent of LH
pulse) Inactivating mutations in KISS1R gene (2003) decreased level
of IP3. In obesity and diabetes cases of HH. Tolson et al :
increased BW + glucose-intolerance + increased leptin levels in KO
KISS1R female mice role of KP system in HH + metabolic diseases.
Absence of spontaneous sexual maturation Low blood levels of
steroids Pathology: Obesity & Diabetes.
Kiss1r KO female MICE Kisspeptin system Glucose-resistance Body
weight Leptin levels No GnRH LH & FSH Sex-steroids Sexual
dysfunctions Role of kisspeptin Sexual dimorphism Adapted from
Talson et al, 2014 Potential therapeutic role: IVF
hCG 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 Conclusion : Kisspeptins role in
neuroendocrine disorders.
Therapy In Vitro Fertilization Ovarian cycle Puberty Physiology
Pathophysiology Hypogonadotropic hypogonadism Diabetes and Obesity
Precocious puberty PCOS Kisspeptin system Thank you for your
attention !