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Cell communication II: endocrine and reproduction 3-14-2016 Hormone (hormoa; to excite) was first assigned by Ernest Henry Starling in 1905 “The chemical messengers which, speeding from cell to cell along the blood stream, may coordinate the activities and growth of different parts of the body” Fifth stages of endocrinology • Recognition of the gland or organ as one producing internal secretion for physiological regulation. • Methods of detecting internal secretion (bioassay). • Preparation of extracts leading to a purified hormone. • The isolation, identification and synthesis of pure hormone. • Pathway biology: receptor, signal transduction and cellular responses. Chemical signal: proteins or small molecules Blood stream Long distance Slow response: seconds to minutes 16_12_cortisol.jpg Chapter 13 Text Art Back Home Back to Text Art Menu Gene regulation by the thyroid hormone receptor Three key questions will be discussed in this lecture • Why many hormone’s secretions are pulsatile? • What is the mechanism of estrogen induced LH surge? • Why menstru How it happen? Why it happen? Optogenetics – the basic concept • Express a light-activated ion channel (isolated from bacteria) in a specific sub-population of neurons • Illuminate neurons to modulate activity Requirement of pulsatile GnRH secretion to stimulate pulsatile LH secretion PNAS | December 23, 2014 | vol. 111 | no. 51 | 18387–18392 Representative 24-h GH concentration and secretion profiles from a man (left) and a woman (right). The Journal of Clinical Investigation 102, 153–164; 1998 J. Sleep Res. (2004) 13, 251–255 Why pulsatile insulin secretion? Diabetes 61, 2269–2279, 2012. In human: this is a continuous process to keep hormone level constant. What happen to the LH when estrogen positive feedback control LH secretion? What causes the switch from negative to positive feedback control? Is GnRH neuron the target of estrogen regulation? No! The GnRH neuron has no estrogen receptor. How to identify the target cells and the messages to mediate estrogen’s dual regulation? Schematic representation of the key pathway underlying estrogen positive feedback in the rodent. BRAIN RESEARCH REVIEWS 57 (2008) 277 – 287. Over 800 G protein coupled receptor (GPCR) were found in human genome Cloning the gene. Looking for the possible function. What is the ligand of GPCR? GPR54 was cloned as orphan receptor Looking for the ligand. How? Tissue distribution. Set bioassay to purify ligand. Kisspeptin! What is kisspeptin? Structural features of human kisspeptins, generated by cleavage form a common precursor, the prepro-kisspeptin. Suppress metastasis of human melanoma Manuel Tena-Sempere Hum. Reprod. Update 2006;12:631639 © The Author 2006. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: [email protected] The GPR54 gene as a regulator of puberty. N Engl J Med. 2003 Oct 23;349(17):1614-27. GPR54/kisspeptin and GnRH/LH GPR54/kisspeptin neuron First hypothesis and current view for the central control of the HPG axis by the Kiss1 system. Leonor Pinilla et al. Physiol Rev 2012;92:1235-1316 ©2012 by American Physiological Society Three key questions will be discussed in this lecture • Why many hormone’s secretions are pulsatile? • What is the mechanism of estrogen induced LH surge? • Why menstruation? Why menstruation? • Clean sperm carried pathogen. • Energetics more favorable. • To avoid maternal/fetus conflict Menstruation: spontaneous decidualization • Hypothesis 1: SD evolved for early protection against invasive fetal tissues • Hypothesis 2: SD evolved for embryo selection Prevent mesnstruation and ovulation High level of E and P Keep 黃體 active CGH urine RU486: competitive inhibitor of the progesterone receptor (progesterone antagonist or antiprogestins) Birth control pill: combination of estrongen and progesterone. Mode of Action: prevent the pituitary from secreting LH and stop ovulation. Usage: take the pills for 21 days and stops for 7 days. The fall in steroid levels triggers menstrual flow.