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Laboratory Medicine and Pathobiology
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LECTURE SEVEN: INTRODUCTION TO THE BIOCHEMISTRY OF HUMAN DISEASES PRINCIPLE ENDOCRINE GLANDS  Brain region: (1) Hypothalamus; (2) Pituitary gland  Neck region: (1) Parathyroid glands; (2) Thyroid gland  Abdominal region: (1) Adrenal glands;(2) Pancreas  Groin region: (1)Ovaries (female);(2) Testes (male) HYPOTHALAMUS  Releasing and Inhibiting Hormones (these are the hormones TESTIS that control the pituitary to secrete or inhibit certain  Testosterone hormone production or secretion): o Thyrotrophin-releasing hormone (TRH) o Somatostatin o Gonadotrophin-releasing hormone (GnRH) o Corticotrophin-releasing hormone (CRH) o Growth hormone-releasing hormone (GHRH) o Prolactin-inhibiting factor (dopamine) PITUITARY (the different sides of the pituitary (anterior or posterior) produce different products – these control the peripheral endocrine glands to release certain hormones) (they are made by the hypothalamus and then stored in the posterior pituitary)  Anterior Pituitary: o Thyroid-stimulating hormone (TSH) o Luteinizing hormone (LH) o Follicle-stimulating hormone (TSH) o Growth hormone (GH) o Prolactin (PRL) o Adrenocorticotrophic hormone (ACTH)  Posterior Pituitary: o Vasopressin or antidiuretic hormone (ADH) o Oxytocin THYROID (these are the peripheral endocrine glands): oThyroxine (T4) oTriiodothyronine (T3) oCalcitonin PARATHYROID (these are the peripheral endocrine glands): oParathyroid hormone ADRENAL  Adrenal Cortex: o Mineralocorticoids (Aldosterone) o Glucocorticoids (Cortisol) o Adrenal Androgens  Adrenal Medulla: o Catecholamine: Epinephrine and norepinephrine (adrenaline and noradrenaline) PANCREAS  Glucagon (from α cells)  Insulin (from β cells)  Somatostatin (from δ cells) OVARY  Estrogens  Progesterone HORMONES – BIOCHEMICAL REGULATORS (they can control lots of biological functions)  Can be classified based on how they act  Endocrine: hormones are secreted into the blood vessel, and carried to distant target cells, such as anterior pituitary hormone ACTH, acts on adrenal (the BLOOD is the carrier to the rest of the body)  Paracrine (they function in the nearby cells): hormones are secreted locally, and act on nearby cells, such as glucagon (from α cells) acts on pancreatic β cells  Autocrine (they act on themselves): hormones are secreted locally, and act on the originating cells, such as 1,25(OH)2vitD (can also function as endocrine and paracrine) from prostate and pancreas  Neuroendocrine and Neurotransmitter: hormones are secreted from neural axon terminals, such as epinephrine and dopamine CONTRL OF THE ENDOCRINE SYSTEM – BY FEEDBACK AND RECEPTOR REGULATION  Feedback: oNegative: e.g. hypothalamus-pituitary-thyroid axis oPositive: e.g. at a particular point in the menstrual cycle, estrogen on LH surge (can also act in a positive feedback manner – it increase the release of the hormones) (The downstream hormones can go back to the upstream endocrine glands to tell them when there is too much or too little – it inhibits the pituitary and the hypothalamus)  Receptor: o Reversible reaction of hormones with their receptors, H + R ⇌ HR o Hormonal specific receptors (they only recognize their corresponding hormones) oTissue specific locations of receptors oDown-regulation of receptors (when there is too much hormone then the receptors can be internalized)  Cell surface receptors and intracellular signaling pathway (they bind to the peptide hormones and pass on the signal through signalling pathways) oE.g. receptors for insulin, GH, PTH, TSH, LH (there are different types of receptors located in different places) oRapid response (their response is very fast)  Intracellular receptors and gene regulation (they bind to the small molecules such as steroids and thyroid hormones) oCytosolic or nuclear, function as hormone-regulated transcription factors, e.g. steroids, T4, 1,25(OH)2vitD oRelatively slower response (slow mechanism – they have to go through the transcription of genes) HYPOTHALAMUS HORMONES:  The hypothalamus is the producer off some hormones and induces the anterior pituitary to release others (it sends the signal to the pituitary via the portal system)  Releasing: TRH, CRH, GnRH, GHRH  Inhibiting: Dopamine & Somatostatin HYPOTHALAMIC FACTORS REGULATE ANTERIOR PITUITARY FUNCTION Hypothalamus GnRH CRH GHRH Somatostatin TRH (has some Dopamine (Inhibits the minor release of bothstimulation on of these) the release of the prolactin) + + + - + - Anterior Pituitary LH/FSH ACTH GH TSH Prolactin Targets Gonads Adrenal cortex Liver & other Thyroid Breast & other tissues tissues Androgens, Estrogens Cortisol IGF-1 T4, T3 (act on the gonads for the production of these) ENDOCRINE DISORDERS  Terminology: o Hyper, hormone above normal level o Eu, hormone within normal level o Hypo, hormone below normal level  Examples: o Oversecretion, e.g. gigantism where a pituitary adenoma overproduces growth hormone (in kids tumors can induce the production of too much GH from the pituitary) o Undersecretion, e.g. primary hypothyroidism (not enough release of the thyroid hormone) o Failure of hormone responsiveness, e.g. Pseudohypoparathyroidism (if the receptor fails then there can be low response – they don’t have low levels of parathyroid hormone – it is actually high just the receptor levels are low and cannot respond) o Abnormal hormone metabolism, e.g. 5α-reductase enzyme deficiency caused abnormal male external genitalia development (biological genotype males appear as female; there is the deficiency of the enzymes in the metabolic pathway and hence the final hormonal product cannot be produced efficiently VARIABLE CONCENTRATION OF HORMONE IN BLOOD STRESS RESPONSE: EPISODIC SECRETION: -E.g. prolactin – venipuncture can increase this (they are scared of the needle) - Up and down, up and down – there is no real pattern CIRCADIAN RHYTHM: - e.g. cortisol and GH release – they are different in the night and in the early morning (the pituitary hormones are released in accordance with the circadian rhythms)  A single blood hormone measurement may have little clinical value (this is due to the variations in the measurements with time) INVESTIGATION OF ENDOCRING DISEASES  Dynamic tests (this is a functional test): following stimulation or inhibition, testing hormonal response and feedback regulation to demonstrate the abnormality of hormone secretion. (give them drugs to increase or inhibit the hormone – then look at the downstream hormone production – if we see the normal response then the pathway is normal the patient
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