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Assist prof. of Medical Physiology • To do its action, the hormone must bind to specific molecules on the cells called receptors. • Hormone receptors are 2 types according to its location; Cell surface or cell membrane receptors Intracellular receptors – Water soluble hormones e.g. peptide hormones, catecholamines bind to cell membrane receptors on the surface of target cells 1. Activation of a membrane-bound enzyme. 2. Rise of intracellular Ca++ concentration: 3. Increase in cell membrane permeability to Na+, K+ and Cl-. • Membrane-bound enzymes include adenyl cyclase • Activation of this enzyme generates a intracellular 2nd messenger (e.g. cyclic AMP) → biological response • The hormone-sensitive adenyl cyclase system has 3 components: i) The receptor:, stimulatory or inhibitory (Rs or Ri). ii) G protein: guanine nucleotide (GTP) – binding protein (Gs or Gi). iii) Catalytic component (C): enzymatically converts Mg2+-ATP to cyclic AMP. 3. Catalytic subunit 1. Receptors 2. G protein • It is a guanine nucleotide – binding protein • It may be Gs or Gi a) Gs mediate the action of the hormones that stimulate adenylyl cyclase activity, b) Gi mediates the action of hormones that inhibit adenylyl cyclase activity. • Gs and Gi are heterotrimers comprised of a unique -subunit (s or i) and similar and subunits. Adenyl-cyclase system Catalytic subunit Receptor G protein γ β C-AMP Activate enzymes Binding of the hormone to the receptor activate G-proteins dissociate the α-subunit change the activity of membrane-bound enzyme "second messenger mediate the action of the hormone – This occurs by 2 mechanisms: i- Increase Ca++ influx, – by activating ligend gated Ca++ receptors. ii- Release of Ca++ from – endoplasmic reticulum, – mitochondrial membrane. • ↑ free cytosolic Ca++ produce the following: 1. Changes in cell motility 2. Contraction of ms cells. 3. ↑ed release of secretory proteins. 4. Activation of regulatory enzymes. 5. Ca++ binds to specific calcium – binding proteins, such as; Calmodulin in smooth ms Troponin C in skeletal ms • Binding of hormone to its membrane receptors ↑es membrane permeability to Na+, K+ and Cl. Cytoplasmic Receptors Steroid Hormones e.g. vit D and retinoids Nuclear Receptors Thyroid Hormones Mechanisms of interaction of lipophilic hormones, such as steroids and thyroid 1. Neural control or neurosecretion 2.Direct innervation 3.Feedback control 4.Blood Level of substances 5.Cytokines – It is a secretion released by a nerve cell & reaches the endocrine glands via blood vessels or nerve fibres. Example 1. Hypothalamic releasing & inhibitory hormones is an example of this type of control 2. Post pituitary hormones are released from terminals of the hypothalamohypophyseal tract. Hypothalamic releasing and inhibitory hormones Posterior pituitary hormones •Usually done by autonomic fibres e.g. sympathetic control of the adrenal medulla Negative Feedback Most common Positive Feedback Less common Trophic Gland A ++ Target Gland B __ - Hypothalamus CRH Pituitary g. ACTH Adrenal cortex Glucocorticoids Significance: 1. Prevent overstimulation of the target glands by the tropic hormones. 2. Adjust the rate of hormone secretion according to the body needs. 3. Maintain hormone blood level relatively constant. Trophic Gland A ++ Target Gland B ++ • Less common • When a target gland hormone (B) is increased, it will increase the rate of secretion of its pituitary tropic & hypothalamic releasing hormones (A) • This relation increases the target gland hormone more and more. • When the target gland hormone reaches sufficient level negative feedback returns again to reduce the hormone to its final level. + Hypothalamus Gn-RH Pituitary g. + LH surge Essential for ovulation LH ovary Estrogens Significance: – Temporary amplification of the biological effects of the hormone. Example: – The link between estrogen and LH – Pre-ovulatory LH surge. Feed-back control system may be: A) Long loop feed-back: – Represents the relationship of target gland H and their ant pituitary trophic hormones. B) Short loop feed-back: – Relation between ant pituitary trophic H and the hypothalamic releasing and release-inhibiting H. Hypothalamus - Short Loop TRH ++ Pituitary G. TSH ++ Thyroid G. T3 and T4 Long Loop a) Organic substances e.g. Blood glucose level and the secretion of pancreatic H. b) Inorganic substances e.g. blood Ca+2, Na+,K+. Blood Ca+2 level and parathyroid and calcitonin hormones. Blood Na & K level and aldosterone. Plasma inorganic substances determines the blood osmolarity, that affect the hypothalamic release of ADH. Def: • Cytokines are small proteins produced by various cell types in different physiological and pathological states. • Cytokines modulate endocrine functions by acting on: • the endocrine glands and • on the target tissues. Example: – Cytokine hormones (e.g., leptin) produced by adipocytes also called adipokines. – Leptin • suppresses GH through stimulation of somatostatin, • suppresses gonadotropins and • stimulates the pituitary–adrenal axis.