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