Lecture 1 – BSCI447 EndocrinologyDr. Tammatha O’BrienOverview- exocrine glands have ducts that lead to the external environment (sweat gland, mammary glands, glands secreting digestive enzymes)- endocrine glands are ductless, secrete into blood streamo Primary endocrine glands Hypothalamus Pituitary Pineal Thyroid & parathyroid Thymus Adrenal Pancreas Gonadso Secondary endocrine glands Heart Kidneys GI tract Skin Adipose tissue- Endocrine system differs from the nervous system, although some neurotransmitters can acts as hormonesNervous Endocrinesecreted by neuron endocrine cellacts on neuron, muscle or gland most cell typessignal neurotransmitter hormonetravels across synapse via bloodstreamonset of effect immediate delayedduration of effect brief longFeedback loops- most hormones are regulated via negative feedback loops; end product and/or effect stop the stimulus- example of positive feedback loop and pathology:o heart attack causes portion of heart tissue to die, which forces heart to compensateo heart is working harder; increases oxygen demando heart must meet this demand, heart rate increaseso heart develops more muscle mass, causing it to work harder, incr O2 demand and cycle continueso treated w/ β-blockers to make slower, more forceful beatso athletes get to rest because the stimulus ends; allows for angiogenesis (increased formation of vasculature to the heart)Classic hormone interactions1. antagonism: the effects of two hormones oppose eachotherex: insulin & glucagon on blood glucose2. Additive: effects of hormones favor each other and sumex: growth hormone, thyroid hormone, testosterone3. Synergism: effects of hormone favor each other but net effect is greater than sumex: glucagon, cortisol, and epinephrine on blood glucose4. Permisseveness: one hormone is needed for another to exert its effectsex: thyroid hormone is permissive for epi b/c it causes expression of adrenergic receptorsPrimary disorders are caused by an abnormality in the endocrine organ that secretes the hormone.Secondary disorders are abnormality of the tropic hormone of anterior pituitary.Tertiary disorders result from abnormality originating in hypothalamus (very rare).Hydrophilic hormones bind receptors on cell surface, whereas lipophilic hormones (steroid hormones) diffuse plasma membrane and bind internal receptors.Response depends on concentration of hormone, # of receptors, and affinity.- down regulation occurs when excess hormone is present- up regulation occurs when little hormone is present*Androgen Insensitivity Syndrome*- genetic disorder causing defective cell receptors for androgens (testosterone)- body does not respond to testosterone, defaults to female appearance- no menses, although this can get confusing in highly trained female athletes who have low cholesterol and typically do not menstruateReceptor Types- enzyme-linkedo tyrosine kinase is common- G-protein-coupledo Gs, Gq, Gi- Channel-linked/ligand gatedo Fast: receptor and channel are the same proteino Slow: receptor is coupled to the channel GPCRs- ligand binds, causing conformational change- alph subunit dissociates and activates enzyme, channel, etc- causing amplification cascadeGs – Stimulatory – activates adenylyl cyclase, which increases [cAMP].Gq – activates phospholipase C, which cleaves PIP2 into IP3 and DAG.Gi – Inhibitory – inhibits adenylyl cyclase, and thus decreases [cAMP].Phosphodiesterase degrades cAMP, can cause signal to end. Second messengers- Calciumo Induces muscle contraction Changes electric potential Binds calmodulin to activate protein kinaseo Stored in mitochondria, smooth ER and boneo Supplements can lead to increased menstrual cramping or deregulated heart rate; vitamin D needed for Ca uptake- IP3 induces calcium release- Second messengers allow amplification of signal from one hormone, one receptorReceptor agonists bind to receptor and mimic normal response.Receptor antagonists bind receptor but produce no response. Ex: Endorphins bind mu receptors to produce analgesia. Morphine is agonist, so it produces the same effect, thus is used as a “pain-killer.” Nalaxone (aka Narcan) is a mu receptor antagonist. Heroin is a derivative of Morphine, thus narcan is used to treat heroin