1. Enzyme Carbohydrates Lipids Proteins / amino acids
Nucleic acid / nucleotides
Enzyme
Metabolism
Replication
Transcription
Translation
Hormones
Transmission of genomic information

2. Hormones

3. INTRODUCTION
The term hormone originally referred to chemical signaling substances synthesized by specialized cells in endocrine glands before being released into the blood. The blood transports them to their target organs, where they exert specific physiological and biochemical effects.

4. Classification of Hormones based on chemical nature
Protein or peptide hormones: insulin, glucagon
Steroid hormones: sex hormones
Amino acid derivatives: epinephrine, thyroxine

5. Classification of Hormones by Mechanism of Action
I Hormones that bind to Intracellular Receptors
Androgens
Calcitriol (1,25[OH]2-D3)
Estrogens
Glucocorticoids
Mineralocorticoids
Progestins
Retinoid acid
Thyroid hormones (T3 or T4)

6. II Hormones that bind to Cell Surface Receptors
A. The second messenger is cAMP:
a2-Adrenergic catecholamine
β-Adrenergic catecholamine
Adrenocorticotropic hormone (ACTH)
Angiotensin II
Antidiuretic hormone (ADH)
Calcitonin (CT)
Chorionic gonadotropin, human (hCG)
Corticotropin-releasing hormone (CRH)
Follicle-stimulating hormone (FSH)
Glucagon
Lipotropin (LPH)
Luteinizing hormone (LH)
Melanocyte-stimulating hormone (MSH)
Parathyroid hormone (PTH)
Somatostatin
Thyroid-stimulating hormone (TSH)

7. II Hormones that bind to Cell Surface Receptors
B. The second messenger is cGMP:
Atrial natriuretic hormone (ANF)
Nitric Oxide (NO)

8. C. The second messenger is Calcium or Phosphatidylinositols (or both):
II Hormones that bind to Cell Surface Receptors
C. The second messenger is Calcium or Phosphatidylinositols (or both):
Acetylcholine (muscarinic)
α1-Adrenergic catecholamine
Angiotensin II
Antidiuretic hormone (ADH, vasopressin)
Cholecystokinin （pancreozymin ）
Gastrin
Gonadotropin-releasing hormone (GnRH)
Oxytoin
Platelet-derived growth factor (PDGF)
Substance P
Thyrotropin-releasing hormone (TRH)

9. D. The second messenger is a Kinase or Phosphatase Cascade:
II Hormones that bind to Cell Surface Receptors
D. The second messenger is a Kinase or Phosphatase Cascade:
Chorionic somatomammotropin (CS)
Epidermal growth factor (EGF)
Erythropoietin (EPO)
Fibroblast growth factor (FGF)
Growth hormone (GH)
Insulin
Insulin-like growth factor (IGF-I, IGF-II)
Nerve growth factor (NGF)
Platelet-derived growth factor (PDGF)
Prolactin (PRL)

10. GENERAL MECHANISM OF HORMONE ACTION
· The first step in hormone action is the binding of the hormone to specific macromolecules in the cell, so-called hormone receptors.
· These receptors can either be located intracellularly or in the cell membrane, and membrane-bound receptors in turn fall into several distinct classes.

11. Classification of hormones by action mechanism is as follows
Group I Hormone that binds to Intracellular Receptors
Group II Hormone that binds to Cell Surface Receptors
A.     The second messenger is cAMP
B.     The second messenger is cGMP
C.     The second messenger is Ca++ and/or
Phosphoinositides
D. The second messenger is Kinase or
Phosphatase

12. Table 44-2. General features of hormone classes (Harper)
Group I Group II
Types steroids polypeptides
iodothyronines proteins
calcitriols glycoproteins
retinoids catecholamines
Solubility Lipophilic Hydrophilic
Transport proteins Yes No
Plasma half-life Long (hs to ds) Short (minutes)
Receptor Intracellular Plasma membrane
Mediator Receptor-hormone complex cAMP
cGMP
Ca2+
metabolites of complex
phosphoinositols
kinase cascades

13. Location of Receptor
Classes of Hormones
Principle Mechanism
of Action
Cell surface receptors (plasma membrane)
Proteins and peptides, catecholamines and eicosanoids
Generation of second messengers which alter the activity of other molecules - usually enzymes - within the cell
Intracellular receptors (cytoplasm and/or nucleus)
Steroids and thyroid hormones
Alter transcriptional activity of responsive genes

14. Second Messenger Examples of Hormones Which Utilize This System
Cyclic AMP
Epinephrine and norepinephrine,glucagon, lutenizing hormone, follicle stimulating hprmone, thyroid-stimulating hormone, calcitonin,parathyroid hormone, antidiuretic hormone
Protein kinase activity
Insulin, growth hormone, prolactin, oxytocin, erythropoietin, several growth factors
Calcium and/or phospho-inositols
Epinephrine and norepinephrine, angiotensin II, antidiuretic hormone, gonadotropin-releasing hormone, thyroid-releasing hormone.
Cyclic GMP
Atrial naturetic hormone, nitric oxide

15. Structure of Intracellular Receptors

16. The image depicts a pair of glucocorticoid receptors (blue and green on the top) bound to their DNA hormone response element (bottom).
The consensus sequence of the hormone response element in this case (called a glucocorticoid response element) is GGTACANNNTGTTCT, where N is any nucleotide.

17. MEMBRANE-BOUND RECEPTORS
There are three known classes of cell-surface receptor proteins:
(1) Ion-channel-linked
     (2) G-protein-linked
(3) Enzyme-linked

18. (1) Ion-channel-linked receptors
Also known as transmitter-gated ion channels, are involved in rapid synaptic signaling between electrically excitable cells. This type of signaling is mediated by a small number of neurotransmitters that transiently open or close the ion channel formed by the protein to which they bind, briefly changing the ion permeability of the plasma membrane and thereby the excitability of the postsynaptic cell. These receptors belong to a family of homologous, multipass transmembrane proteins.

19. (2) G-protein-linked receptors
Act indirectly to regulate the activity of a separate plasma-membrane-bound target protein, which can be enzyme or an ion channel.
The interaction between the receptor and the target protein is mediated by a third protein, called a trimeric GTP-binding regulatory protein (G protein). These G-protein-linked receptors belong to a large superfamily of homologous, seven-pass transmembrane proteins - G Protein Coupled Receptors (GPCRs)

20. (3) Enzyme-linked receptors
When activated, either function directly as enzymes or are associated with enzymes. Most are single-pass transmembrane proteins, with their ligand-binding site outside the cell and their catalytic site inside.
Compared with the other two classes, enzyme-linked receptors are heterogenous, although the great majority are protein kinases, or are associate with protein kinases, that phosphorylate specific sets of proteins in the target cell.

21. There are five classes of enzyme-linked receptors
Receptor Guanylyl Cyclases
Receptor Tyrosine Kinase
Tyrosine-Kinase-associated Receptors
Receptor Tyrosine Phosphatase
Receptor Serine/Threonine Kinases

24. INTRACELLULAR RECEPTORS
Most steroid and thyroid hormones are transported in plasma bound to carrier proteins. The protein-bound hormones (HP) are in dynamic equilibrium with small amounts of free hormones (H) that diffuse by a passive mechanism into cells.

25. INTRACELLULAR RECEPTORS
In most instances the principal form of the hormone secreted into plasma (cortisol, progesterone, aldosterone, estradiol) undergoes no further metabolism within the cell and is responsible for hormone action within the target cell.
Other hormones (thyroxine, testosterone) undergo chemical conversion to more active forms (triiodothyronine and dihydrotestosterone).

26. INTRACELLULAR RECEPTORS
H binds to specific receptor proteins (R) in the cytoplasm or nucleus to form a hormone-receptor complex (HR).
The hormone-receptor complex has the capacity to bind to specific regulatory sequences in DNA (so-called hormone regulatory elements (HRE), and thus acts to control the rate of transcription. As the result of this interaction with DNA new messenger RNAs (mRNAs) are formed, and the synthesis of cytoplasmic proteins is enhanced. The cytoplasmic proteins, in turn, mediate the effects of the hormone.

28. Model of glucocorticoid steroid hormone regulation.

29. Classification of Hormones based on histological origin
Hypothalamus
Pituitary
Thyroid
Adrenal gland
Gastrointestine
Sex gland
Pancreas

31. HYPOTHALAMIC HORMONES
1. GRH: Growth Hormone Releasing Hormone
2. GRIH(SS): GH-inhibiting hormone
(Somatostatin)
3. TRH: Thyrotropin Releasing Hormone
4. PRF: Prolactin Releasing factor
5. PIF: Prolactin Inhibiting factor
6. GnRH: Gonadotropin Releasing Hormone
7. CRH: Corticotropin Releasing Hormone

32. Pituitary Hormones
Hypothalamic hormones regulate the anterior pituitary
The anterior pituitary produces many hormones that stimulate various physiological processes

33. thyroid
Uterine
Adrenal gland
Distal convoluted tubule
corpus luteum
folliole
Bone, liver
Mammary gland
melanocyte
melanin
analgesic

34. supraoptic and paraventricular nuclei

35. Pituitary Hormones Three Categories
The Growth Hormone-Prolactin-Chorionic Somatomammotropin Group
The Glycoprotein Hormone Group
The Pro-Opiomelanocortin Peptide Family

36. Hormone Major Physiologic Effects Anterior Pituitary
Major target organ(s)
Hormone
Major Physiologic Effects
Growth hormone
Liver, adipose tissue
Promotes growth (indirectly), control of protein, lipid and carbohydrate metabolism
Thyroid-stimulating hormone
Thyroid gland
Stimulates secretion of thyroid hormones
Anterior Pituitary
Adrenocorticotropic hormone
Adrenal gland (cortex)
Stimulates secretion of glucocorticoids
Prolactin
Mammary gland
Milk production
Lutenizing hormone
Ovary and testis
Control of reproductive function
Follicle-stimulating hormone
Ovary and testis
Control of reproductive function
Posterior Pituitary
Antidiuretic hormone
Kidney
Conservation of body water
Oxytocin
Ovary and testis
Stimulates milk ejection and uterine contractions

37. Growth Hormone (GH)
Substances that regulate cell differentiation and organ development.
Included are many of classic hormones and various growth factors.
Growth and development is dependent upon cell cycle, which is coordinated by the actions of Hs and GFs.

38. Growth Hormone (GH) A. Synthesis & Structure
Regulation from hypothalamus by Somatocrinin
(GH-RH) and Somatostatin (GH-IH)
Physiological feedback by IGF-1
B. The GH Receptor
C. Physiologic & Biochemical Actions
Direct Action
Indirect Action

39. Growth Hormone (GH)
Somatomedins: IGF-1 (Insulin-like Growth Factor-1) & IGF-2
Produced by liver by somatotrophin
They mediate the indirect actions of somatotrophin.
IGF-1 is more important than IGF-2.
They share 62% of sequence homology.
They have structure similar to that of proinsulin

40. Growth Hormone (GH) Pathophysiology GH-insufficiency
Hypothalamic dwarfism: no GH-RH
Primary pituitary dwarfism: Genetic or tumor or GH incapable of stimulating IGF-1
Endo-organ resistance
idiopathic dwarfism: insensitivity (receptor) of the liver to GH
African pygmies: normal GH / low IGF-1

41. Prolactin (PRL: Lactogenic Hormone, Mammotropin, Luteotropic Hormone)
A. Synthesis & Structure
B. The Prolactin Receptor
C. Physiologic & Biochemical Actions
D. Pathophysiology
Chorionic Somatomammotropin (CS, Placental Lactogen

42. GROUP II Glycoprotein Hormones
A. The Gonadotropins (FSH, LH, & hCG)
B. Thyroid-Stimulating Hormone (TSH)

43. GROUP III Pro-Opiomelanocortin (POMC) Peptide Family
POMC (241 AA) is the source of several important biologically active substances. POMC can be cleaved enzymatically into the following peptides:
MSH: Melanocyte-Stimulating Hormone
CLIP: Corticotropin-like intermediate peptide

44. GROUP III Pro-Opiomelanocortin (POMC) Peptide Family
A. Distribution, Processing & Functions of the POMC Gene Products
B. ACTH
1.  Structure & Mechanism of Action
2.  ACTH Pathophysiology
C. b-Lipotropin (b -LPH)
D. Endorphins
E.Melanocyte-Stimulating Hormone (MSH)

45. The posterior pituitary contains two active hormones, vasopressin & oxytocin
A. Regulation of Secretion
B. Mechanism of Action
Antidiuretic Hormone (ADH: Vasopressin)
A. Regulation of Secretion
B. Mechanism of Action
C. Pathophysiology

46. Tissue hormone
(COX-3?)
Prostaglandins biosynthetic pathway