BSCMLTEndocrinology Introduction to Hormones

Hormones Introduction, Classification and Receptors

1. ENDOCRINE SYSTEM Dr. Apeksha Niraula Assistant Professor D e partment of Biochemistry Institute of Medicine, TUTH 5/9/2024

2. OBJECTIVES Endocrine System: Basic Concepts Hormone: Classification, Types, Receptors Mechanism of Action of different hormones Hypothalamic-Pituitary System Hypothalamic Hormones

3.  IL-1 from macrophages that stimulates the bound T cell to proliferate and differentiate Insulin, Epinephrine  Autostimulatory release of IL-2 enhances the response of a T cell to IL-1

4.  Endocrine System refers to the collection of glands of an organism that secrete hormones directly into the circulatory system to be carried toward a distant target organ Major endocrine glands: Pituitary gland Thyroid gland Parathyroid gland Adrenal glands Pancreas Pineal gland Ovaries Testes Hypothalamus Gastrointestinal tract Introduction

5.  Reproduction Responses to stress and injuries Growth and sexual development Body energy levels Internal balance of body systems Bone and muscle strength Areas governed by the Endocrine system

6. Hormones A hormone is a chemical transmitter Released in small amounts from glands, and is transported in the bloodstream to target organs or other cells Hormones are chemical messengers, transferring information and instructions from one set of cells to another

7. I.  Lipid hormones Derived from cholesterol Adrenocortical hormones, sex hormones and calcitriol The cholesterol-derived hormones contain a steroid nucleus and are lipophilic in nature Readily traverse the cell membrane of their target cells and interact with the cytoplasmic receptors II. Amino acid hormones Produced by enzymatic modification of an amino acid molecule Epinephrine and thyroxine are derived from tyrosine molecule Types of Hormones

8. III. Peptide and protein hormones Made up of amino acids, joined by peptide bonds e.g. Thyrotropin releasing hormone: Tripeptide, Antidiuretic hormone (9 amino acids), Glucagon (29 amino acids), parathormone (84 amino acids), and growth hormone (191 amino acids) IV. Glycoprotein hormones Consists of peptide chain to which carbohydrate moieties are covalently attached The latter are necessary for the biological activity of these hormones Examples include pituitary hormones (TSH, LH and FSH), and chorionic gonadotropin (hCG) of placental origin

9. Biosynthesis of Hormones Biosynthetic mechanisms for hormones are diverse Some hormones are initially synthesized as large precursor proteins which are converted to the biologically active forms by removal of specific peptide sequences

10. Peptide hormones: Circulate in the blood in free form, unbound to any transport protein [Polar/Hydrophillic] Steroid hormones and the Thyroid hormones : are predominantly hydrophobic in nature: cannot circulate in blood entirely in an unbound form Mostly transported to their site of action by carrier proteins, where they exert their action and are inactivated by further metabolism Transport

11. Physiological and biochemical effects of a given hormone are elicited only in a specific tissue, known as its target tissue A target tissue has specific receptors with which the hormone interacts Hormone-receptor interaction triggers a series of events that subsequently lead to elicitation of the biological effects of the hormone Target Tissue Concept

12. For example: Target tissue for thyroid-stimulating hormone (TSH) is the thyroid gland, where this hormone stimulates synthesis and secretion of the iodothyronines (T3 and T4) Similarly, adrenal cortex, the target tissue for ACTH, responds to ACTH by increasing steroidogenesis

13. Blood levels of the target tissue hormones (e.g. thyroid gland) have an effect (mostly inhibitory) on the S ecretory activities of either the hypothalamus or pituitary Short feedback loop and long feedback loop Relies on a precise signalling helps to maintain the circulating plasma concentration of the hormones to the required levels Such feedback mechanism is best illustrated by the hypothalamo-pituitary-target gland axis Feedback Concept

14. Receptors: cell-associated recognition molecules that play a crucial role in the hormone action The receptors for water-soluble hormones (peptides, proteins, or glycoproteins) are present on the cell surface Interaction of hormones with receptors stimulates certain molecules namely second messengers , which mediate biochemical functions intracellularly The receptors for lipophilic hormones such as the steroids and the thyroid hormones are located intracellularly General Characteristics Hormone Receptors

15.  Structure of Receptors Intracellular-Receptors: Lipophillic/ Steroid Hormones Cell-Surface Receptors: Hydrophilic/peptide hormones Second Messenger

16. Down Regulation: Reversible process Covalent Modulation: Regulation of Receptors

17. Hormone Receptors and Diseases I. F i rst category : Diseases in which binding of the hormone and the receptor is impaired; in some cases, no binding has been detected II. Second category: Antibodies of IgG class, directed against a specific hormone receptor, have been detected The antibodies may  (a) block the action of the hormone (b) mimic hormone binding (Graves’ disease), or (c) enhance receptor turnover (myasthenia gravis) III. Third category: Receptor regulation is defective

18. Mechanism of Action of Hormones Hormones have been classified in two major groups based on their mechanisms of action: I. Group I Comprises the lipophilic hormones that are derived from cholesterol and the thyroid hormones (exceptions—T3 and T4) These hormones interact with cytoplasmic or nuclear receptors respectively The hormone receptor complex itself acts as an intracellular messenger and directly influences the gene expression

19. II. Group II Comprises the peptide, protein, and glycoprotein hormones These hormones bind with the surface receptors, located on the plasma membrane of the target cells The hormone-receptor interaction transmits a signal across the membrane, that results in elevation of the intracellular level of an intermediary molecule, the so called second messenger (the hormone itself is the first messenger) Group IIa hormones: cAMP as the second messenger Group IIb hormones: cGMP as second messenger Group IIc hormones : Calcium or phosphatidylinositides (or both)

20. A significant group of hormones is secreted by peripheral endocrine glands in response to signals from the brain The brain structures responsible for initiating such signals are the Hypothalamus Pituitary gland Hypothalamus-pituitary System

21. Pituitary gland/ hypophysis: oval organ; weight 0.6 g Encased in the body cavity of the skull (sella turcica) below the brain Demarcated into two parts: Anterior pituitary (Adenohypophysis) (80% of the gland) Posterior pituitary (Neurohypophysis) Pituitary gland lies below the hypothalamus and is connected with it via the pituitary stalk, which contains a complex array of axons and blood vessels

22. Control of hypothalamic-pituitary target organ axes

23. Thank You