DENT Fun. I - Peptide & Steroid Hormones

What are the 3 Classes of Hormones?

- Amino Acid-Derived

- Peptide

- Lipid-Derived

Hormones from the Hypothalamus

- Gonadotropin Releasing Hormone (GnRH)

- Thyroid Releasing Hormone (TRH)

- Corticotropin Releasing Hormone (CRH)

- Dopamine/Prolactin Inhibiting Hormone (PIH)

- Growth Hormone Releasing Hormone (GHRH)

GHRH

Growth Hormone Releasing Hormone

- Released by the Hypothalamus

- Controls release of GH from the anterior pituitary

TRH

Thyroid-Releasing Hormone

- Targets the Anterior Pituitary for release of TSH

____ is a Small Peptide Hormone.

TRH

What is the primary structure of TRH?

Glu-His-Pro-NH2 x4

Tripeptide that is ~12 amino acids long

Hormones from the Pituitary

- Growth Hormone (GH)

- Thyroid Stimulating Hormone (TSH)

- Adrenocorticotropic Hormone (ACTH)

- Follicle Stimulating Hormone (FSH)

- Luteinizing Hormone (LH)

- Prolactin

- ADH

- Oxytocin

ADH

Antidiuretic Hormone

- Upregulates aquaporin channels in the collecting ducts of nephrons, retaining water

- Released by Posterior Pituitary

Growth Hormone

Targets the Liver and Bone, increasing metabolism and bone growth

____ and ____ are both Large Protein Hormones.

Growth Hormone/Insulin

Small Peptide Hormones

Are at a low concentration and soluble enough to be transported unbound to any soluble carrier

Large Protein Hormones

Carried by soluble proteins that resemble the protein receptor the Hormone binds at its target

Where are Peptide Hormones taken after binding to their receptor?

The Lysosome to be broken down

Oligopeptides

12-20 amino acids

Polypeptides

20-40 amino acids

Alpha-Cells

Pancreatic cells that secrete Glucagon

Beta-Cells

Pancreatic cells that secrete Insulin

Delta-Cells

Pancreatic cells that secrete Somatostatin

Insulin

- 2 chains bound by 2 disulfide bonds; 1 of the chains has an intra-chain disulfide bond for a total of 3

- Facilitates the uptake of Glucose into cells via upregulation of Glucose transport proteins

- Glycogen Synthesis

- Lipogenesis

Insulin Synthesis

(1) Preproinsulin synthesis in RER

(2) Cleavage of presignal = Proinsulin

(3) Proinsulin is transported to the Golgi to be packaged

(4) Proinsulin cleavage = Insulin

(5) Exocytosis of Insulin via Ca2+

Insulin Receptor

- Protein composed of a tetra-peptide (2 Alpha + 2 Beta Subunits)

- When bound, activates Tyrosine Kinase inside the membrane

How does Insulin move Glucose into Cells?

(1) Insulin binds to receptor

(2) Signaling pathway triggers Glut4 to move to the plasma membrane

(3) Transporter fuses to membrane and will take up Glucose as long as Insulin keeps coming from Beta-Cells

What are the 2 subunits of a G-Protein?

- Beta-Gamma Subunit

- Alpha-Subunit

General cAMP Mechanism

(1) Stimulatory G-Protein is bound by external receptor

(2) Internal Alpha-Subunit replaces GDP with GTP, activating the subunit

(3) Active Alpha-Subunit turns Adenylyl Cyclase (AC) on

(4) AC converts ATP into cAMP

(5) GTPase on Alpha-Subunit hydrolyzes GTP into GDP, turning it off

G-Proteins can also be inhibitory (T/F)

True

Know G-Proteins at different tissues??

cAMP can be broken down before it enters a cascade. What enzyme breaks cAMP down?

cAMP Phosphodiesterase (PDE)

cAMP typically activates ____ in the first step of most cascades.

Protein Kinase A (PKA)

PKA

Tetrameric protein that, when stimulated by cAMP, dissociates into 3 subunits. 2 of these are active catalytic subunits.

Ca2+/Calmodulin Mechanism

(1) Hormone binds to cell membrane receptor

(2) Through G-Protein it a. opens cell membrane Ca2+ channels and b. releases Ca2+ from the ER

(3) Increased intracellular [Ca2+]

(4) Ca2+ binds to Calmodulin

(5) Ca2+ Calmodulin Complex produces physiologic response

Utilizes PKC instead of PKA

What 2 Hormones utilize the Ca2+/Calmodulin Mechanism?

- ADH

- TRH

Peptide Hormones

Hormones composed of short chains of <12 amino acids

- Polar

- Largely use G-Proteins via PKA or Ca2+-DAG Pathway

Peptide Hormones are synthesized as ____ or ____.

prehormones/preprohormones

Peptide Hormones are stored in ____.

membrane bound granules

What are the 3 types of Steroid Hormones?

- Glucocorticoids

- Mineralocorticoids

- Androgens/Estrogens

Glucocorticoids

Cause...

- Increased metabolism of carbs, lipids, and proteins

- Immunosuppressive Effects

Cortisol

Mineralocorticoids

Promote reabsorption of Na+ and excretion of K+ in the Kidneys, affecting TBV

Aldosterone

Androgens/Estrogens

Sex Hormones

Testosterone/Estrogen

Steroid Synthesis is stimulated by the ____.

Pituitary

What are the 3 major locations of Steroid Synthesis?

- Adrenal Gland

- Testes

- Ovaries

Steroids are made from ____ in the ____.

cholesterol/mitochondria

ACTH

Adrenocorticotropic Hormone

- Stimulates the Adrenal Glands

Adrenal Cortex

Produces...

- Cortisol

- Aldosterone

- Androgens/Estrogen

Adrenal Medulla

Produces NE/E

Corticosteroids

P450 Enzymes

Enzymes responsible for the modification of the Cholesterol tail via mixed function oxidation, producing Steroid Hormones

What is needed for Cholesterol Modification?

- P450 Enzymes

- NADPH

- O2

Glucocorticoid Functions

[Cortisol]

- Increase [Glucose] via Gluconeogenesis

- Suppress immune System

- Aid in fat, protein, and carb metabolism

- Decrease bone formation

Cushings Syndrome

Condition caused by prolonged exposure to high [Cortisol]

- Bone Loss

- Muscle Wasting

Mineralocorticoid Function

[Aldosterone]

- Na+ retention/K+ excretion via Kidney reabsorption of at the distal tubules and collecting ducts; Causes increased water retention and an increase in BP

Conns Syndrome

Increased production of Aldosterone in the Adrenal Glands

Addison's Disease

Aldosterone Insufficiency

Androgens

[Testosterone]

- Growth of muscle mass and bone density

- Secondary male characteristics

Estrogen

- Metabolism

- Secondary female characteristics

- Decreased bone resorption

Steroids require ____.

carrier proteins

What are the 3 Carrier Proteins of Steroids?

- Transcortin

- SHBG

- Albumin

Transcortin

Corticosteroid and Cortisol binding globulin

SHBG

Sex Hormone Binding Globulin

- Glycoprotein that binds Testosterone and Estradiol

- Produced by the Liver, Brain, Uterus, and Vagina

Influence bioavailability of sex hormones, therefore, their effect on the body

Albumin

Binds both corticosteroids and sex hormones

Steroid Hormone Mechanism of Action

(1) Steroid binds receptor in Cell and releases the blocking protein

(2) Steroid-Receptor Complex enters nucleus and modifies transcription of genes

Some protein-hormone complexes bind enhancer regions. The enhancer regions must be able to reach the ____ to influence transcription.

promoter region

Steroid Hormones are derived from the ____ ring.

cyclopentanoperhydrophenanthrene

Peptide Hormones can be administered orally (T/F)

False; Steroid Hormones can though