Basics of Endocrinology

1. Basics of Endocrinology Hasan AYDIN, MD Yeditepe University Medical Faculty Endocrinology and Metabolism

2. Definitions • Endocrinology- the study of hormone and glandular abnormalities • Hormones-biologically active substances secreted by glands • Endocrine- hormones that have a biological effect far away • Paracrine- hormones that have a biological effect nearby • Autocrine- hormones that have a local effect

3. Endocrine System Neuroendocrine System Nervous System Secretory cell Neuron H H H Target

5. Paracrine Actions • Paracrine-actions • sex steroids inthe ovary • angiotensin II in the kidney • platelet-derived growth factor released by platelets. • Juxtacrine actions • somehematopoietic growth factors

6. Autocrine Action • Insulin released by the pancreatic islet B cells • Somatostatin can inhibit its own release from pancreatic D cells

7. Hormones • Substances released by endocrine glands and transported through the bloodstream to tissues where they act to regulate specific functions. • These actions are mediated by binding of the hormone to receptor molecules. • Allosteric effectors that alter conformation of the receptors to which they bind.

8. Functions of Hormones • Growth and development: Thyroid, GH, Sex Steroids, Cortisol • Reproduction: Estrogen, Testosterone, FSH, LH, Thyroid • Homeostasis: Thyroid, Cortisol • Changes in environment: Cortisol, Thyroid Aldosterone

9. Hormones can interact with each other Gluco neo genesis Protein synthesis Temp Metab HR Organ growth Sex steroids T-4 GH Skeletal growth

10. Hormone Classification • Proteins- TSH, insulin, PTH • Amino acids-thyroid hormones (T3 and T4), epinephrine • Steroids-cortisol, aldosterone, testosterone

11. Mechanism of Action of Hormones • Circulate in blood stream bound to transporter proteins or free • Free hormone is the active hormone • Enter cells to alter biological activity

12. I I I I Hormone Action: peptide and cathecolamines R TSH TSH TSH R 2nd messenger protein T-4 effect

13. T-3 R R T-3 Hormone Action: Steroid, Thyroid T-3 TBG T-3 R T-3 Increased HR β-receptors

14. Hormone Regulation • Feedback loops • Circadian rhythms • Receptor specificity • Receptor concentration

15. Phenomenon of Negative Feedback

16. Phenomenon of Positive Feedback

17. Feedback Regulation of the Anterior Pituitary: Hypothalamus - - Short Loop Feedback - ? Long Loop Feedback + - Pituitary + Target Organ

18. Feedback Mechanisms: Rhythms Circhoral rhythmsare ''about an hour,'' Circadian rhythms are ''about a day'' Circatrigantan rhythms are''about a month,'' Circannual rhythms are ''about ayear.'‘

19. Endocrine Rhythms ACTH LH GH 0800 2000 0800 0800 2000 0800 0800 2000 0800 Cortisol TSH Testosterone 0800 2000 0800 0800 2000 0800 0800 2000 0800

20. The Subunit Confers Specificity α- Subunit β - Subunits hCG LH TSH FSH

21. Precursors of Hormones Precursor Type of compound Example of hormone Protein Growth hormone Peptide ACTH Protein Amino acid Thyroxine Cortisol Steroid Cholesterol 1,25 OHD3 Modified amino acid Epinephrine Tripeptide TRH Amino acid Retinoid Retinoic acid Eicosanoid Prostoglandin E1 Fatty acid

22. Receptors

23. Receptors • Cellular proteins that have bifunctional properties of both • Recognition • Signal activation

24. Catecholamines Prostoglandins ACTH Glukagon PTH TSH LH Somatostatin Insulin GH TGF-b Receptors • Cell surface receptors:

25. Receptors Nuclear receptors: • Steroid hormones • Vitamin D • Thyroid hormones • Retinoids

26. Regulation of Responsiveness to Hormones Effector1 Effector2 Response Hormone Receptor ± ± ±

27. Interaction Between Hormone Response System H1 R1 G1 E1 Range of Possible Pathways H2 R2 G2 E1

28. Classification of Hormones: Types of Ligands: • Agonist • Antagonist • Partial agonist-partial antagonist • Mixed or Heterologous Agonists-Antagonists

29. Classes of Hormone Action Glucocorticoid Agonist Cortisol Mineralocorticoid Progestin Partial agonist-antagonist Progesterone Glucocorticoid Mixed agonist-antagonist Estrogen Tamoxifen Estrogen Mineralocorticoid Spironolactone Antagonist Androgen

30. Neuroendocrinology • Neurotransmitter • Synthesized in the cell body of the neuron • Travels down the axon • Stored in synaptic vesicles • Released upon depolarization • Mediates synaptic transsmission between two neurons • Paracrine action

31. Nicotinic cholinergic Serotonergic Dopaminergic GABA Muscarinic Alfa 1 adrenergic Alfa 2 adrenergic Beta 1 adrenergic Beta 2 adrenergic Neurotransmitter Receptors

32. Catecholamines TRH Dopamine CRH CGRH Somatostatin GnRH VIP Gastrin Secretin Cholecystokinin Neurotransmitter and Hormones

33. Hypothalamic-Pituitary Relations • The hypothalamus regulates • temperature, • appetite, • thirst, • sexual behavior, • defensive reactions such as rage and fear, • body rhythms • The hypothalamus contains two types of neurosecretory cells • Neurohypophysial neurons traverse the hypothalamic-pituitary stalk and release vasopressin (ADH) and oxytocin from nerve endings in the posterior pituitary • Hypophysiotropic neurons release hormones into the median eminence and thence into the hypothalamic-pituitary vessels.

34. Hypothalamic- Anterior Pituitary Relations • Stimulating hormones (releasing hormones) • TRH, • GnRH, • CRH, • GHRH, • Prolactin-releasing factorand • ADH • Inhibitory hormones • Somatostatin and • Dopamine.

35. Precursor Phenomenon(Prehormones)

36. Biosynthesis of Hormones: Precursors Pro-Opiomelanocortin (POMC) β-LPH N-Terminal Peptide ACTH LPH β-Endorphin α-MSH

37. Bind to plasma protein Steroid Thyroid hormones Vitamin D GH Vasopressin Oxytocin Free Peptid hormones (ACTH, insulin, glucagon, PTH etc) Hormone Transport

38. Regulation of the Endocrine System • Hormone concentration • Production rates • Delivery to the target tissue • Degradation • Freestanding

39. Actions of Hormones • Developmental effects • Cell growth & cancer • Central nervous system effects • Effects on metabolism • Effects on cardiovascular & renal function • Effects on mineral & water metabolism • Effects on skeletal functions • Effects on reproductive function • Release of other hormones • Effects on immunologic functions

40. Clinical Endocrinology • Hypofunction of a gland • Hyperfunction of a gland • Receptor defect • Second messenger defect

41. Endocrine Hypofunction • Congenital defects in hormone biosynthesis • Autoimmune destruction of glands • Surgery or trauma to glands • Infiltration by tumors, infection

42. Endocrine Hyperfunction • Hormone secreting pituitary tumor • End organ secreting tumor • Autoimmune disease • Inflammation/Infection • Iatrogenic/Facticious • Ectopic hormone secreting tumor

43. Causes of Hypo or Hyperfunction

44. Defects in Sensitivity to Hormones • Partial or complete resistance to the hormone • Secondary hormone hypersecretion

45. Down-regulation

46. Assessment of Glandular Activity • Measure the end organ hormone • Measure the pituitary regulating hormone • Suppression tests-to evaluate for hormone overactivity • Stimulation tests-to evaluate for underactivity • Imaging studies

47. ThePlayers • Other endocrine organs • endothelial vascular cells • adipocytes • heart • bone • liver • kidney • ????

48. Conclusions • Hormones are essential for normal growth, development, metabolism, energy, reproduction etc. • Hormones are tightly regulated by multiple systems • Both over and underproduction of hormones leads to clinical disease