Overview of Lecture: Endocrine systems Read: Text ch 45 Bullet Points: • endocrine system • Para-Neuro-Endo Sys • Prostaglandins-COX-Pain • Feedback & Fever • Receptors & 'Meaning‘ • Ancient Origins • Classic Hormones • Steroid Hormones • Endocrine Disrupters • Peptide-Protein Hormones • Caffeine - G-coupled • Hypothalamus-Pituitary • PheromonesCOX-1 maintains prostaglandin synthesis in the stomach, kidneys, and platelets. Non-selective NSAIDs inhibit COX-1 & COX-2 COX-2 inhibitors selectively inhibit COX-2 COX-2 maintains prostaglandin production predominately in inflamed tissue PGE2 & ↑ risk of heart attacks! VR1 PGE2 {note: G-coupled}VR1which then release ‘cytokines’ incl. interleukins IL-1 & IL-6. into local tissue and circ. sys. Locally: recruit immune cells & inflammation At neurons in anterior hypothalamus which regulate body temp ‘set point’: act as ‘endogenous pyrogens’ by increasing synthesis of prostaglandin E2 (PGE2) which acts on hypothalamic neurons in a way that increases the regulated temperature 'set point'. Aspirin reduces fever by inhibiting the synthesis of prostaglandins in the hypothalamus. http://plpk04.plpk.uq.edu.au/webtuts/SDL_skin/fever.htm Bits of bacterial antigen (LPS endotoxin) are phagocytosed by macrophage leucocytes. { MΦ }Chemical Signals and modes of action (see ch 11) The distribution of receptors determines which cells ‘get the message.’ Nicotinic acetylcholine Skeletal Motor neuron Parasympathetic: vagusmelatonin: widespread effects; Ducrest et al. 2008 Tree 23:502-510 insulin, glucagon (fig 45.12) thyroxine, calcitonin Pituitary: posterior: ADH, oxytocin anterior: GH, ACTH, PRL,MSH TSH,LH,FSH Adrenal medulla: epinepherine norepinephrine cortex: aldosterone, cortisol estrogens, progesterone androgens mysterious ‘thymosins’ important in early development of the immune system parathyroid hormone see Fig 45.20 Hypothalamus: ‘releasing hormones’ control anterior pituitary + many new signaling molecules that fall between endocrine & paracrine, ex: atrial natriuretic hormone (right atrium of heart), erythropoietin (kidneys), Vitamin D (skin) leptin (fat), ghrelin (stomach), etc.Supplemental stimulation of existing receptors upregulates existing genes for muscle proteins {-FB ‘side-effects’ later} note: lipid-soluable means water-insoluable; a carrier protein suspends these in aqueous plasmaBPA is used in the manufacture of plastics and resins ... used in milk and food containers, baby formula bottles ... dental resins ... BPA leaches from these materials ... ... wildlife and humans are affected by environmental exposure to hormonally active chemicals at levels previously considered to be irrelevant. {data mostly from mice}Prenatal Exposure to Phthalates is Associated with Reduced Masculine Behavior in Boys Shanna H. Swan and Bernard Weiss NIEHS grantees Drs. Shanna Swan and Bernard Weiss report for the first time that prenatal exposure to phthalates causes reduced masculine behavior in boys. This finding adds to the growing list of health effects associated with phthalates and other endocrine disrupting compounds found in plastics. Mothers, whose urine had been analyzed for phthalates in mid-pregnancy, completed a questionnaire including the Pre-School Activities Inventory used to assess gender differences in play behavior. The results show that concentrations of … phthalate metabolites in the mothers' urine were statistically associated with decreased masculine play behavior in boys who were an average of 5 years-old at the time of the assessment. There were no strong associations for … with girls' play behavior. Although based on a relatively small sample (N=74 boys), the overall findings exhibit concern that environmental chemicals have the potential to alter androgen-responsive neurologic development in humans. Citation: Swan SH, et al. Prenatal phthalate exposure and reduced masculine play in boys. Int J Androl. 2010 Apr;33(2):259-69.What NIEHS is Doing on Endocrine Disruptors • Flame Retardant Linked to Decreased Thyroid Hormone Levels in Pregnant Women • Solutions to Arsenic Groundwater Contamination • Arsenic-Related Mortality in Bangladesh • Prenatal Exposure to Phthalates is Associated with Reduced Masculine Behavior in Boys • Phthalate Exposure Alters Children's Behavior and Cognitive Function • Flame Retardants Linked to Reduced Human Fertility • Bisphenol A (BPA): Expanding Research to Impact Human Health • Bisphenol A Reduces the Effectiveness of Chemotherapeutics • Dioxins in Food Chain May Cause Poor Milk Production • PCBs May Alter in utero Neonatal Brain Development • Questions and Answers about the Draft National Toxicology Program Brief on Bisphenol A • Phthalate Exposure May Extend Pregnancy • Consumption of Foods with High Soy Content is Associated with Lower Sperm Concentrations in Men • Expert Panel Evaluation of Soy Infant Formula (51KB) • Effects of Organochlorine Compounds on Menstrual CyclesSignal-receptor binding on outside alters the ‘tail’ of the receptor inside, setting off a cascade of biochemistry inside, often involving phosphorylation … … generally changes the metabolism of cells but can alter transcription. see ch 11 for more info on receptors & transductionThe LD-50 for coffee varies from 50 to 200 cups. {note double negative: caffeine inhibits inhibition of adenylyl cyclase by adenosine} Caffeine has a withdrawal syndrome featuring headache and nausea. Caffeine is used to relieve headaches. less cAMP: adenosine Note the - ! - sleepy, less dopamine in brain {dopamine & addiction later} X{ADH is also a neurotransmitter in brain aka vasopressin – more later}What do you suppose happens when blood testosterone (or mimic) levels are raised by external supplements? http://www.dotpharmacy.com/upanabol.html Fig 14.14 Hormone therapy: A dangerous elixir? Nature 431, 500 - 501 (30 September 2004) Testosterone therapy jacks up vigour, sex drive and mental acuity - or so proponents claim. But … testosterone replacement might increase the likelihood that latent cancerous cells in the prostate gland will transform into tumours. …(cortisol) Interactions Between