Physio E4: Endocrine

What are the 3 classes of hormones?

peptides, amines, steroids

Peptides:

stored as active hormones until a stimulus triggered its secretion

Amines:

stored in vesicles awaiting a stimulus for release; Thyroid hormones require carrier

Steroids:

synthesized from cholesterol, not stored in vesicles and rapidly diffuse once synthesized due to high lipid solubility

Plasma hormone concentration depends on

rate of hormone secretion and elimination, extent of hormone binding to plasma proteins

More hormones bound =

less active; need the free version

Negative feedback:

occurs when a hormone, or response to a hormone, directly inhibits further secretion of that hormone

primary negative feedback

disorder with secretion by the target gland

secondary negative feedback

disorder with secretion by pituitary gland

tertiary negative feedback

disorder with secretion by the hypothalamus

circadian pattern

day/night pattern of secretion (ex:cortisol and GH)

pulsatile pattern

bursts of hormone release

constant secretion leads to

built up resistance to the hormone

half-life

time it takes to reduce concentration of hormone in half

metabolic clearance rate

volume of plasma cleared of the hormone per minute

Hormones can be removed from the plasma by

metabolism or binding to tissues, hepatic excretion, renal excretion

What type of hormones are not protein bound and have a faster onset of action for shorter periods of time?

water soluble hormones (peptides and catecholamines)

What is sensitivity determined by?

number of receptors (up regulate or down regulate)

Activation of the receptor via hormone results in either:

-generation of intracellular second messengers

-changes in gene transcription and translation

What is the role of second messengers for peptides and catecholamines?

amplify the hormonal signal within the target cell

activate G proteins

What different pathways do second messengers activate?

-cAMP

-DAG

-IP3

What breaks down cAMP?

phosphodiesterase enzyme (PDE)

PDE type 3 breaks down cAMP in what type of muscle?

cardiac muscle

Milirone inhibits PDE type 3 therefore increasing what in cardiac muscle?

contractility and vasodilation

In presence of Ca2+, DAG activates ….

Proteine Kinase C → changes in cell behavior

IP3 causes release of …

Ca2+ from ER stores

Eicosanoids

group of secondary messengers; differ form others because they are hormones themselves

(prostaglandins, prostacyclins, thromoxanes, leukotrienes)

Why are steroid and thyroid hormone effects slow?

they occur due to changes in gene transcription and translation

What is considered the master gland due to its ability to control secretions of several target endocrine glands?

pituitary

What controls the secretion of pituitary hormones?

factors from hypothalamus (hypothalamic-pituitary axis)

6 major peptide hormones secreted from the anterior pituitary:

GH, TSH, ACTH, FSH, LH, Prolactin

Which anterior pituitary hormone is not secreted in response to a hypothalamic hormone?

Prolactin

What control is prolactin under?

negative feedback by prolactin inhibitory factor (PIF) aka dopamine

Hypothalamic hormones

CRH, GHRH, GnRH, TRH, PRH

All hormones in HPA exhibit what type of release?

pulsatile superimposed on circadian rhythm of secretion

Why is pulsatile release important?

to maintain sensitivity of anterior pituitary cells

What does exposure to constant levels of hypothalamic hormones cause?

down regulation and loss of sensitivity

What hormone is the most important endocrine regulator of final body size?

GH (indirectly through IGF1)

GH causes acute metabolic effects that oppose effects of insulin by…

-lipolysis in adipose tissue

-reduced glucose uptake in muscle

-gluconeogensis in liver

When is the largest pulsatile secretion (70% ) of GH?

first 2 hours of deep sleep

Acute stress stimulates GH secretion causing…

increase blood glucose concentration

How does short term hypoglycemia stimulates GH release?

ghrelin

What serves as a potent stimulus for GH secretion?

long term starvation

Control of GH is by negative feedback from what?

IGF-1

What is the purpose of having the majority of IGF-1 bound to proteins in the blood?

extends half life and provides constant levels despite fluctuations of GH

The posterior pituitary gland secretes…

neurohormones ADH and oxytocin; released via exocytosis

Where is ADH formed?

supraoptic nucleus

Where is Oxytocin formed?

paraventricular nucleus

Oxytocin is important for?

uterine contraction, cervical dilation, milk let-down/ejection, maternal behavior

Which function of oxytocin is under the influence of a positive feedback loop?

cervical dilation

Thyroid hormones T4 and T3 play major roles in what?

overall control of metabolic rate

What is the major protein in the thyroid gland?

Thyroglobulin (T6)

Primary Thyroid hormone effects

-increase BMR

-Induce gluconeogenesis

-coordinate normal growth and development

Majority of thyroid hormones are

T4

Which Thyroid hormone has high biologic activity?

T3

A majority of T3 is derived from what?

deiodination of T4

Thyroid hormones exert long-lasting effect through?

gene transcription and translation

How do thyroid hormones increase BMR?

-stimulate catabolism and anabolism of TRGs and PTN → generates body heat

-Brown adipose tissue → generates heat (neonates)

-increase expression of B-adrenergic receptors

Negative feedback is exerted by __ controlling thyroid hormone production

T3 and T4

What are the three distinct zone of Adrenal Cortex? What do they secrete?

-zona glomerulosa : aldosterone

-zona fasciculata : cortisol

-zona reticularis : androgens

What does the adrenal medulla secrete?

catecholamines

What type of cells are in the adrenal medulla? what do they secrete?

chromaffin cells; Epinephrine + small amount of NE

Mineralcorticoids synthesize what adrenocortical hormone?

aldosterone

Glucocorticoids synthesize what adrenocortical hormone?

cortisol

Sex steroids synthesize what adronocorical hormones?

androgens, estrogens, progestins

What does steroid synthesis start with? What is the rate limiting step?

cholesterol; conversion of cholesterol to pregnenolone

Weak androgen cells lack enzymes to produce testosterone and estrogens. They produce ___ instead

progesterone → used to synthesize cortisol and aldosterone

If 21a-hydroxylase is absent, Progesterone make what instead?

androstenedione

What must be present to synthesize aldosterone?

aldosterone synthase; stimulated by Angio II

What synthesizes the cleavage of cholesterol?

ACTH in the adrenal cortex

What must be present to synthesize cortisol?

17a-hydroxylase

__ is secreted in response to virtually all forms of stress

(ex: trauma, infection, illness, temp change, and mental stress)

Cortisol (in absence even minor illness can be fatal)

Actions of cortisol:

mobilize glucose, AA, and fatty acids; resist inflammatory and immune responses

How does glucocorticoid increase blood glucose?

-stimulate hepatic gluconeogenesis

-mobilize AA from muscle

-reduce cellular metabolism of gluocse

-reduce sensitivity to insulin →glucose stays in blood

HPA cascade for cortisol

CRH → ACTH → cortisol

Cortisol is a negative feedback system for

CRH and ACTH (ACTH is most potent)

What type of control pattern does cortisol follow? When are levels the highest?

circadian rhythm; levels highest in the morning → alert and active

If you have low cortisol =

ACTH high; POMC high

POMC is a precursor to

ACTH and MSH

What is the primary action of ACTH?

stimulate cortisol release

Aldosterone secretion is primarily controlled by what?

Angiotensin II; weakly by ACTH

Main action of Aldosterone

Na+ reabsorption and K+ secretion at distal tubule

What happens in absence of aldosterone?

severe Na+ depletion and K+ retention → fatal

What is the most important stimulus for aldosterone secretion?

renin-angiotensin system (High K can also stimulate)

What is secreted from juxtaglomerular cells in response to LECV?

renin

What stimulates renin release?

reduced distension of renal afferent arteriole

low GFR and BF

baroreceptors detect low BP

Renin increases concentrations of

angiotensin II and aldosterone

Where does Angio II bind to receptors to stimulate aldosterone secretion?

zona glomerulosa

The synthesis of Epi and NE are derived from

Tyrosine under ACTH and SNS

Tyrosine pathway

Tyrosin → DOPA → dopamine → Nor Epi → Epi (via cortisol)

The release of catecholamine is controlled by what

CNS

What binds to nicotinic cholinergic receptors on chromaffin cells?

Ach

What are the 5 major receptor types of Catecholamines and their role?

a1 → coupled to G PTN → Inc Intracellular Ca2+

a2→ suppress cAMP

B1,2,3 → increase cAMP

Affinity of Epi and NE

Epi > NE for B1 and B2; Epi = NE for a

Role of catecholamine short-term response

inc CO, bronchodilation, blood glucose

SA node receptor and response

b1 → inc HR

AV node and His-Purkinje receptor and response

b1 → inc conduction speed

Bronchiolar smooth muscle receptor and response

b2 → relaxation

Sphincters receptor and response

a1 → constriction

Detrusor wall receptor and response

b2 → relaxation of bladder