Lecture 18 If you need clarification about the material: Read before our discussion Make sure you have your flowcharts/drawings with you Your notes page 110 All effects on effector cells are via second messengers systems: muscarinic AChR and norepinephrine (adrenergic) receptors ACh acts on muscarinic receptors to decrease heart rate nAChR- fast EPSP and in the heart mAChR-mediated slow IPSP (opening K channels) and decreased heart rate IPSP Endocrinology The study of chemical messengers, hormones, secreted from glands into the blood stream to alter the function of distant target tissues Comparing the endocrine and nervous systems Hormones Released into blood Variable acting distance Low concentration (< nM) Higher binding affinity of receptor Intracellular amplification: Second messengers Diverse signaling Mostly slow onset and long duration Multiple factors involved in release Neurotransmitters Released near receptors Short acting distance Higher concentration (ÁM) Lower binding affinity Some intracellular amplification Precise signaling Mostly fast onset (respond first) Depolarization triggers release Both coordinate cellular activity to maintain homeostasis The concentration of hormone in the blood is under feedback control and is determined by 4 processes: Synthesis Release Transport Removal Hormones differ in all four categories, depending on their chemical nature Hormones are divided into 3 general chemical classes Peptide or protein: wide-range number of amino acids. Most hormones belong to this group. Amines: derivates of the amino acid tyrosine Steroids: derivates of cholesterol Hormone synthesis Steroid hormones are hydrophobic in nature. Synthesized primarily in the adrenal cortex and gonads. Synthesis of steroid hormone (e.g. estrogen) is based on demand. Hormones secreted from the adrenal cortex. The final product depends on the level of specific enzymes Androgens: testosterone-like hormones Synthesis of steroid hormones in the gonads male female Synthesis and release of steroid hormones Cannot be stored Synthesis on demand Slow onset of effect Protein and peptide hormones are hydrophilic in nature and can be stored in vesicles Prohormone: An inactive form of hormone that is typically activated by enzymatic cleavage of a polypeptide segment Amines Thyroid hormones: T3 (triiodothyronine) and T4 (thyroxine) are hydrophobic in nature. Synthesized by the thyroid gland. Catecholamines: epinephrine, norepinephrine and dopamine are hydrophilic in nature. Synthesized by the adrenal medulla. Thyroid hormones are synthesized as part of a large glycoprotein, thyroglobuline, that is stored in the lumen of follicles. T3 and T4 are hydrophobic in nature Release Steroid hormones: the rate of release is the same as the rate of synthesis Peptides, proteins and catecholamines are stored in membrane bound vesicles (Ca-dependent exocytosis) . Thyroid hormones are released via a complex process (more later) Factors that affect hormone release Transport Hydrophilic hormones are soluble in the plasma Hydrophobic (lipophilic) hormones (steroids and thyroid hormones) are bound to transport protein. Albumin is a non-specific carrier of lipophilic hormones. The binding to albumin reduces the rate of hormone degradation and removal from plasma Removal Peptides, proteins and catecholamines are cleared from plasma: seconds to minutes Glycoprotein and steroid hormones: hours Thyroid hormones: days The effect of a hormone can outlast its presence Hydrophilic hormone-receptor interaction Hydrophilic hormones: protein/peptide, catecholamines bind to receptors on the surface of target cells. Typically trigger effects via second messenger systems. In most cases, act/modify (e.g. phosphorylation) existing proteins and the effect takes places within a short timescale. Hydrophobic hormone-receptor interaction Binds to nuclear receptors (sometimes via cytoplasmic receptors) Results in synthesis of new proteins. Slow onset: effects take place within long timescale. Not suitable for emergency situation Mechanisms of hormone actions Different receptors and regulatory actions of hydrophilic and lipophilic hormones Actions of specific hormones Regulation of hormone secretion by central neurons The hypothalamus Integrates somatic and visceral sensory information and initiates hormonal response Relationship between the hypothalamus and the pituitary glands The function of the hypothalamo-pituitary portal vessels Connection via capillary network Tropic hormone Hormone that stimulates the secretion of another hormone and typically promotes the growth of the hormone-secreting gland Sequential pattern of regulating hormone release Tropic hormones GHIH Adrenocorticotropic Hypothalamic-anterior pituitary system
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