NO is cell-permeant and activates what? 

cytosolic guanylyl cyclase 

From where do agonists exert their influence? 

Outside the Cell 

Protein kinase action vs. protein phosphatase action 

p. kinases phosphorylate proteins

p. phosphatases catalyze the removal of phosphates 

what activates members of the protein kinase C family? 

Ca++, diacylglycerol, certain membrane phospholipids and some breakdown products of membrane phospholipids

True or False:

Calmodulin is found in all cells 

True 

What are the steps leading up to the exchange of GDP for GTP in the activation of a heterotrimeric G-protein? 

1. Hormone or agonist binds to membrane receptor, which causes conformational change.

2. Activated receptor accociates with inactive G-protein bound to GDP.

3. Binding to receptor causes G protein alpha subunit to release GDP in exchange for GTP. 

What are the steps in G-protein activation following binding of GTP to the protein's alpha subunit? 

1. The GTP-bound alpha subunit  dissociates from beta/gamma subunits and hormone receptor.

2. Activated G protein associates with effector protein (eg. adenyl cyclase) and activates it to generate second messenger (eg cAMP).

3. Intrinsic GTPase of alpha subunit converts GTP to GDP, causing inactivation and reassociation of alpha subunit with beta/gamma subunits.  

Gs  G-proteins are activated by receptors for what compounds?

Epinephrine

Norepinephrine

Glucagon 

What is the effector for Gs proteins? 

Adenyl cylclase 

Gi G-proteins are activated by receptors for which compounds? 

Norepinephrine

Adenosine 

Prostaglandins

Opiates 

What is the effector (target) for activated Gi proteins? 

Adenyl cyclase 

Gq proteins are activated by receptors for which compounds?

Acetylcholine

Epinephrine

(targets Phospholipase C) 

Cholera toxin interferes with which step of G-protein activation/inactivation? 

Cholera toxin prevents hydrolysis of GTP in the activated Gs alpha subunit through the addition of an ADP-ribosyl group.  

The presence of ________ greatly inhibits the enzymatic activity of PKA 

its 2 regulatory subunits

- cAMP binds to the regulatory subunits, allowing the catalytic subunits to dissociate and phosphorylate target proteins on particular serine and threonine residues. 

Myosin light chain kinase and phosphorylase kinase are examples of? 

Calmodulin-dependent protein kinases 

_________ is covalent modification of the protein, which changes its properties and most often leads to activation. 

Phosphorylation 

4 examples of Serine/Threonine kinases 

 PKA

 PKG
PKC
MLCK

Axons from the hypothalmus project directly into the ____________, where they release hormones from nerve terminals into the blood. 

posterior pituitary 

_________ hormones are synthesized from cholesterol. They include ______, _______, _______,_______,________, _______. 

Steroid hormones include:

cortisol, aldosterone, androgens, estrogens, progestins, vitamin D. 

__________ hormones are synthesized from tyrosine and iodide and include ____ and _____. 

Thyroid hormones include thyroxine (T4) and triiodothyronine (T3).

True or False:

 ADH and OCT are released by the anterior pituitary. 

Diabetes insipidus is characterized by a failure to secrete suffcient amounts of what hormone? 

ADH (vasopressin)

This can lead to excessive water loss through hypotonic urine (polyuria) and drinking large volmes of water (polydipsia).  Treatment with ADH provides rapid relief.

Tropic hormones made and secreted by the anterior pituitary include: 

"FLAT PG"

FSH

LH

ACTH

TSH 

Prolactin

GH 

True or False:

GH can inhibit insulin uptake and lipolysis 

False.

It does inhibit insulin uptake, but it enhances (does not inhibit) lipolysis.

Thus GH is diabetogenic (produces diabetes). 

GH works directly on peripheral tissues or through the release of secondary peptide hormones called _____. 

Somatomedins or Insulin-like growth factors (IGF-1 and IGF-2) 

_____ stimulates GH release from the anterior pituitary, while ____ inhibits it. 

GHRH stimulates

Somatostatin inhibits 

______ inhibits Prolactin secretion while _____ enhances it. 

Dopamine or PIF from the hypothalmus is the primary inhibitor. Less important are thyrotropin (TRH) and vasoactive intestinal peptide (VIP).

Estrogen acting directly on mammotrophs of ant. pituitary enhances secretion.  

A. Iodine is moved from the blood into the follicular cells of the thyroid through what kind of transport?

B. By what kind of transport does it move from the follicular cell into the colloid? 

A. Secondary active transport (through I-, Na+ symport)

B. Facilitated diffusion 

Which enzyme catalyzes iodination of Thyroglobulin to make T3 and T4? 

TPO - Thyroid peroxidase 

_________ is the protein precursor which contains the tyrosine residues used to synthesize T3 and T4. 

Thyroglobulin 

True or False:

Only small amounts of T3 and rT3 are secreted by the thyroid. 

True.

Most of the T3 and rT3 are formed from deiodination of T4 in the tissues.

Grave's disease, toxic adenoma, TSH-secreting pituitary tumor, and thyroiditis can all cause _____. 

Hyperthyroidsim 

Liver glycogen can be made available to other tissues via the process of _________ and glucose release. 

glycogenolysis 

Glucose can be made de novo by the conversion of two pyruvate molecules via the process called _________. 

gluconeogenesis 

In the pancreas,

1. Alpha cells secrete ____

2. Beta cells secrete _______

3. D cells secrete ________ 

1. glucagon

2. insulin, amylin

3. somatostatin 

Hsp's are bound to what hormone receptors ?

GRs and MRs (for Cortisol and Aldosterone, respectively) and ARs (for DHT and testosterone) are bound to Hsp's in the cytosol. Binding of the hormones releases the receptors from the heat shock proteins. The new complex then enters the nucleus, dimerizes, and initiates transcription of specific genes.

The major hormones synthesized by the adrenal cortex 

Aldosterone (in Glomerulus)

Cortisol (in fasciculata)

Androgens (in Reticularis) 

Major hormones synthesized by Adrenal Medulla 

Epinephrine and Norepinephrine

(synthesized in chromaffin cells) 

What endocrine organ can be thought of as an enlarged specialized sympatheic ganglion? 

The adrenal medulla 

What are catecholamines derived from?

Name the intermediate compounds. 

Tyrosine } Dopa } Dopamine } Norepinephrine } Epineprine

Limiting step: action of tyrosine hydrogenase in converting tyrosine to dopa 

Epinephrine binds to what and increases what? 

binds to beta 1 and 2 adrenergic receptors and increases cAMP 

Norepinephrine binds to what and increases what? 

binds to alpha 1 and 2 adrenergic receptors and increases intracellular free Ca2+

(through PLC conversion of PIP2 to IP3 and DG)

Nepi also decreases cAMP 

Beta blockers are used to treat what? 

hypertension 

(ACE inhibitors also used) 

Pheochromocytoma are tumors of what organ? 

Adrenal medulla

- produces too much epi and Norepi and so symptoms include high BP, tachycardia, anxiety, headaches, cold sweats, etc 

True or false:

Catecholamines are secreted from the chromaffin cells of the adrenal medulla with the help of carrier proteins 

False

ACh stimulates secretetion directly without help of proteins

- No Time for helpers in the fight or flight response! 

Metabolic actions of Epi and NorEpi 

blood vessels - constrict (Nepi especially)

heart - increase rate and force of contractions

muscle - release of lactate via glycogen breakdown

liver - glycogenolysis and gluconeogenesis

bronchioles - induces pulmonary vasodilation

renin - stimulates renin release which stim. aldosterone, which increase Na+ retent. and BP 

The most distinctive feature of the luteal phase is a 10-fold increase in plasma levels of __________, secreted by the corpus luteum.  

progesterone 

What gonadotropin stimulates which cell?

LH, FSH

Leydig cells, Sertoli cells 

LH acts on Leyding cells 

-increases testosterone production through the cholesterol/pregnenolone pathway

FSH acts on Sertoli cells

- stimulates protein synthesis: inhibin, ABP, P450 aromatase, AMH and 5alpha reductase 

- Both cell types are also sensitive to testosterone 

True or False:

Leydig cells are found in the seminiferous tubules 

False

They are found in the connective tissue outside the seminiferous tubules 

If fertilization of the egg occurs in the luteal phase, declining LH is replaced by _________, secreted by  placental cells. 

HCG - human chorionic gonadotropin  

True or False:

Progesterone is converted to androgens in the Granulosa cells 

False

Granulosa cells lack the CYP17 and 17BetaHD enzymes 

True or False

Estradiol secretion by the dominant follicle feeds back positively to the pituitary and hypothalmus, resulting in LH and FSH secretion. 

True

This positive feedback by estradiol responsible for pre-ovulation surge of FSH and LH 

Theca cells do not have the ________ enzyme, and so cannot convert androgens to __________. 

aromatase

estradiol

Theca cells produce androgens from progesterone, while granulosa cells produce estradiol from androgens. 

True or False

DHEA is synthesized from pregnenelone in the placenta 

False

DHEA comes from fetus or mother because it cannot be synthesized by the placenta, which lacks CYP17

Placenta turns DHEA into estrogens (estradiol)

Name 2 G-proteins that bind to Adenyl Cyclase and activate it to generate cAMP as a second messenger 

Gs and Golf 

The inactivation of cAMP is catalyzed by what enzyme? 

cAMP phosphodiesterase 

-inactivation yields 5'-AMP, which is inactive as a second messenger 

Which class(es) of hormones are derived from tyrosine? 

Thyroid hormones and catecholamines

On which residues are proteins phosphorylated by protein kinases? 

Tyrosine, Serine, or Threonine

(all have OH groups) 

Which classes of hormones are lipophylic? 

Steroids and thyroid hormones 

-These 2 classes are lipophylic, which means they are often bound to proteins (TBG, albumin) and have a longer half-life, making their effects last hours to days as opposed to minutes or seconds, as is the case with hydrophilic catecholamines or peptide hormones.

Sensitivity of a hormone receptor is measured by what?  

The hormone dose giving half the maximal response (EC50)

Diabetes insipidus is caused by a defect in which hormone? 

ADH or vasopressin 

which hormones are secreted into the median emminence? 

RHs (releasing hormones) and IHs (inhibitory hormones) 

What is the other name for the anterior pituitary hormone TSH and what hypothalmic hormone stimulates its release? 

Thyrotropin

Thyrotropin Releasing Hormone (TRH) 

Name three hormones that Somatostatin inhibits the secretion of

GH  (Somatotropin)

insulin

glucagon 

True or False:

Somatomedins from the liver and other tissues exert both long loop and short loop negative feedback to stop the secretion and release of GH. 

True

-somatomedins are also known as Insulin-like growth factors (IGFs) 

True or False:

GH inhibits glucose uptake and enhances lipolysis 

True

-thus GH termed diabetogenic 

What hormone is produced by the intermediate lobe of the pituitary gland? 

Melanocyte-stimulating hormone (MSH, melanotropin) 

Name the actions of LH in both the female and male 

LH in female: stimulates ovulation and luteinization of ovarian follicles

LH in male: stimulates testosterone secretion 

What are the primary actions of FSH in the male and female, respectively? 

Male: stimulates spermatogenesis

Female: stimulates follicle growth 

How are thyroid hormones stored? 

T3 and T4 are stored in the precursor protein iodinated thyroglobulin in an extracellular colloid storage compartment.

Fatty acids feed into __________.

A. glycolysis

B. citric acid cycle 

They do this via the compound _________.

 A. Acetyl CoA

B. Pyruvate 

fatty acids only feed into the citric acid cycle through the compound acetyl CoA. 

_______ activates glucose uptake into fat and muscle and also enhances the conversion of glucose to glycogen in the liver. 

Insulin 

_______ inhibits amino acid release and proteolysis in muscle and inhibits lipolysis. 

Insulin 

________ enhances the breakdown of glycogen and increases the uptake of fatty acids and amino acids. 

Glucagon 

______ is the glucose transporter stimulated by insulin.

A. SGLT1

B. SGLT2

C. GLUT4 

C. GLUT4

main expression of GLUT4 is in the skeletal and cardiac muscle and adipose and other tissues.

SGLT1 and 2 are Na-dependent co-transporters of glucose, expressed in the small intestine and renal tubules, respectively. 

Can insulin levels be normal in Type 1 or Type 2 diabetes? 

Type 2

-Where there is resistance to insulin

Type 1 is a defect in pancreatic beta cells - you don't actually secrete any insulin, so treated with injections.