bio endocrine

Hormones - Classical Definition

Chemical substances synthesized by endocrine glands and transported through the bloodstream

Hormones - Modern Definition

Substances released by one cell that act on another

Autocrine vs. Paracrine vs. Endocrine

Autocrine - same cell

Paracine - adjacent cell

Endocrine - distant cell

Endocrine vs. Exocrine

Endocrine:

- Target is external

- Ducts

- Poorly vascularized

Exocrine:

- Target is internal

- No ducts

- Highly vascularized

Peptide Hormones

Hydrophilic; bind transmembrane receptors; rapid effects

Preprohormone (Rough ER) ➝ Prohormone (Rough ER; signal peptide removed) ➝ still Prohormone (Golgi) ➝ Hormone (Secretory vesicles; glycoprotein, carrier, and hormone are separated)

Vasopressin/ADH

Peptide hormone made in hypothalamus and released by the posterior pituitary that increases water reabsorption in the kidneys, increasing blood pressure

Made up of signal peptide, vasopressin, neurophysin (carrier protein), and glycoprotein

Uses GPCR-AC-PKA pathway to bring aquaporins to the surface of kidney cells, increasing uptake of water

Amine Hormones

Hydrophilic (except T3/T4); some endocrine, some neurotransmitters, some both; catecholamines, serotonin, melatonin, histamine

Steroid Hormones

Hydrophobic; synthesized in smooth ER/mitochondria; synthesized as needed; slow effects (EXCEPTION: cortisol acts non-genomically and works rapidly)

- Mineralocorticoids (kidneys)

- Glucocorticoids (adrenal glands)

- Reproductive hormones (gonads)

Agonist

Binds to receptor and activates it

Antagonist

Binds to receptor and does not activate it

Dissociation Constant

Kd; concentration of ligand where 50% of receptors are bound; low Kd \= high affinity

Law of Mass Action

Receptor will become saturated at high ligand concentrations

Isoforms

Receptors that bind the same ligands but trigger different pathways

Promiscuous Receptors

Receptors that bind multiple ligands, all of which trigger the same response

GPCR Mechanism

1. Ligand binds GsPCR

2. G(alpha)s releases GDP and binds GTP

3. G(alpha)s activates adenylate cyclase

4. Adenylate cyclase converts ATP to cAMP

5. cAMP binds the regulatory unit of PKA, which dissociates, activating the catalytic unit of PKA

6. The catalytic unit of PKA phosphorylates Ser/Thr on protein targets

7. Ser/Thr phoshphatases remove the phosphate groups from the proteins

8. Different ligand binds GiPCR

9. G(alpha)i inhibits adenylate cyclase and the signal is terminated

Types of Receptor Enzymes

- Guanlyate Cyclase

- Receptor Tyrosine Kinase

- Ser/Thr Receptor Enzymes

Gunalyate Cyclase Mechanism

1. Ligand binds receptor

2. Receptors converts GTP to cGMP

3. cGMP activates PKG

4. PKG phosphorylates Ser/Thr on protein targets

Receptor Tyrosine Kinase Mechanism

1. Ligand binds receptor

2. Receptor dimerizes and autophosphorylates

3. Phosphorylated receptors interacts with protein kinases

4. Protein kinases activate Ras (GDP ➝ GTP)

5. Ras activates MAPKKK cascade

Ser/Thr Receptor Enzyme Mechanism

1. Ligand binds Type I TGF-beta receptor

2. Receptor dimerizes with Type II receptor

3. Type II phosphorylates Type I

4. Phosphorylated Type I phosphorylates SMAD protein

5. SMADs enter the nucleus and regulate transcription

Anterior vs. Posterior Pituitary Gland

Posterior pituitary gland is like an extension of the hypothalamus (has its own blood supply) and does not produce any pituitary hormones; it only stores specific hormones made by the hypothalamus

Anterior pituitary gland is like its own organ; connected to hypothalamus by portal vein; produces its own hormones in response to hypothalmic hormone release

Tropic Hormones

Hormones that cause the release of other hormones

Growth Hormone Pathway

GHRH/GHIH (hypothalamus) ➝ GH (anterior pituitary) ➝ IGFs (many tissues)

Growth Hormone Disorders/Complications

- Gigantism (overactive GHRH early in life)

- Acromegaly (overactive GHRH later in life; do not grow taller, but face gets large)

- GH deficiency (dwarfism; treatable with exogenous GH)

- GH receptor insensitivity (dwarfism; difficult to treat)

Prolactin Pathway

PRH/PIH (hypothalamus) ➝ PL (anterior pituitary) ➝ FSH/LH (gonads)

Prolactin Function

Stimulates milk production and development of breast tissue/mammary glands

Thyroid Pathway

TRH (hypothalamus) ➝ TSH (anterior pituitary) ➝ T3/T4 (thyroid)

T3 (active form) and T4 stimulate metabolism

Thyroid Disorders/Complications

- Lack of TSH as fetus (cretinism)

- Hyperthyroidism (Grave's Disease)

Cortisol Pathway

CRH (hypothalamus) ➝ ACTH (anterior pituitary) ➝ cortisol (adrenal cortex)

*Inhibited by GHIH

Pancreas Hormones

Exocrine: pancreatic enzymes and sodium bicarbonate

Endocrine: insulin, glucagon, somatostatin (GHIH)

Insulin vs. Glucagon

Insulin lowers blood sugar

Glucagon raises blood sugar

Islet of Langerhans

Alpha - glucagon

Beta - insulin

Delta - somatostatin

Feedforward Pancreatic Pathway

Glucose receptors in digestive tract trigger CCK to lower blood sugar before digestion even occurs; CCK and stretching of the digestive tract stimulate insulin release from the pancreas

Type I Diabetes Mellitus

Loss of beta cells/no insulin production

Hyperglycemic coma (not enough insulin): heavy breathing, blood pH drops

Hypoglycemic coma (missed insulin): hypothermia

Treatment: exogenous insulin/insulin agonists

Type II Diabetes Mellitus

Insensitivity to insulin/insulin resistance/hyperplasia of pancreatic beta cells

High correlation with obesity, not necessarily causation

Treatment: exercise (immediately decreases insulin resistance, but short-lived)

HPA Axis

CRH (H) ➝ ACTH (P) ➝ Cortisol (A) ➝ Many tissues

Adrenal Gland Hormones

Cortex - corticosteroids, mineralocorticoids