Endocrine 1 Flashcards
What is the endocrine system?
The endocrine system is a series of glands that produce and secrete hormones that the body uses for a wide range of functions
The hormones are secreted into the bloodstream and taken around the body until they encounter their target issue which have their receptors
Differentiate hormones and neurotransmitters?
Hormones- are secreted by the endocrine gland/cell into blood. Only target tissues with the receptors will have a response
Neurotransmitters- are secreted by neurons that diffuse across a small gap to the target cell. Neurons also use electric signals
What are neurohormones?
Are chemicals released by neurons into blood for action on target tissue/cells at distant sites
Distinguish lipid and water soluble hormones
Lipid soluble hormones act within the cell and change gene expression. Act slowly in contrast to peptide hormones
Water soluble hormones bind to receptor on cell membrane and usually involve second messengers. Act faster than steroid hormones
Describe the characteristics of lipid soluble hormones( steroids, thyroid hormones)
Receptors inside the cell, usually in the nucleus
Intracellular action- stimulates synthesis of specific new proteins
Storage- synthesized as needed, exception: thyroid hormones
Plasma transport- attached to proteins that serve as carriers, exceptions: adrenal androgens
Half life: long(hours, days)inversely proportional to affinity for protein carrier
Describe the characteristics water-soluble hormones( peptides, proteins)
Receptors- outer surface pt the cell membrane
Intracellular action- production of second messengers, e.g., cAMP;
insulin doesn’t utilize cAMP, instead activates membrane-bound tyrosine kinase
Second messengers modify action of intracellular proteins. (Enzymes)
Storage- stored in vesicles
-in some cases, prohormone stored in vesicle along with an enzyme that splits off the active hormone
Plasma transport- dissolved in plasma( free, unbound)
Short(minutes) inversely proportional to molecular weight
Explain equilibrium
The liver normally produces proteins that bind lipid soluble hormones e.g. cortisol- binding globulin, thyroid-binding globulin
Lipid soluble hormone circulaating in plasma bound to protein is in equilibrium with a small amount of free hormone
It is the free form that is available to the tissues and thus the free unbound form that normally determine the plasma activity
Note: it is the free form that creates negative feedback
How to calculate”clusters total hormone in blood?
Total hormone in blood= bond+ free
Active hormone= free hormone
Briefly describe hormonal control
There are 3 major mechanism:
- Humoral—> control by substances in the extracellular fluid(ECF)
- Neural—> controlled by nerves at the inner sting gland
- Hormonal—> control by other glands
Note: negative feedback is very important in regulating most endocrine systems
Explain the clearance of hormones
- largest fraction degraded in liver, the kidneys play a significant role
- urine is the primary route of excretion of hormone degraded products
- peptide hormones are degraded mainly by proteases in target tissue. Catabolism of steroid and thyroid hormones makes them soluble in bile and urine
What are the types of endocrine disorders?
Primary and secondary
Primary and secondary can both be further categorized by hyper function and hypo function
What is an endocrine disorder?
Primary disorder means dysfunction originating in the endocrine gland either hyper or hypo-function while secondary disorder indicates a disturbance has occurred causing the gland to secrete more or less of the hormone
Give examples of primary and secondary endocrine disorders
Primary
- Conn’s syndrome—> excess aldosterone from adrenal adenoma
- Central diabetes insipidus—> reduced ADH secretion
Secondary
1. Cushing disease—> pituitary adenoma secreting ACTH resulting in hypercotisolism
What is endocrine hyper function caused by?
- Hormone secreting tumors
- Hyperplasia
- Autoimmune stimulation
- Ectopically produced peptide hormone (ACTH, ADH)
What is endocrine hypofunction caused by?
- Autoimmune disease
- Tumors
- Infection
- Hemorrhage
How are the pituitaries cinnected to the hypothalamus?
Anterior pituitary-vascular connection
Posterior pituitary- neural connection
What are the site of synthesis and release of ADH?
ADH is synthesized by supraoptic(SO) and some paraventricular(PVN) nuclei of the hypothalamus, it is stored and released by the posterior pituitary
What are the actions of ADH?
- ADH increases the permeability of the duct to water by placing water channel (aquaporins) in the lum8nal membrane of the renal collecting duct (V2 receptors)
- ADH also acts via V1 receptors in the vascular smooth smooth muscles to cause contractions
Explain ADH regulation by ECF osmolarity
Osmoreceptors are neurons that respond to increased plasma osmolarity
They synapse with the SO and PVN, to stimulate the secretion of ADH from the posterior pituitary
Osmoreceptors also stimulate the thirst centers within the hypothalamus to allow for the increased consumption of water
An increase of only 1% in the osmolarity of the ECF that bathes the hypothalamic osmoreceptors evokes an increase in ADH secretion
Similarly, a decrease in osmolarity in osmolarity causes decreased ADH secretion
Because the osmolarity is so tightly regulated, it explains why plasma osmolarity is kept very close to 285 mOsm/kg
Explain the ADH regulation by ECF volume
The SO and PVN also receive input from cardiopulmonary mechanism as well as arterial baroceptors
Stimuli arising from these receptors act to chronically inhibit ADH secretion
Decreases in blood volume cause venous and arterial stretch receptors to send fewer signals to the hypothalamus, decreasing the inhibition of ADH secretion
Mechanism usually active in hemorrhage
Give some random ADH facts
- volume receptors are less sensitive than osmoreceptors and a change of 10-15% in volume is required to produce a measurable change in ADH
- ADH is also stimulated by angiotensin 2 (part of the RAA system)
Note ingesting alcohol or being in a weightless environment causes suppression of ADH.In weightlessness, there is shift of blood from limbs to the abdomen and chest, this results in greater stretch of the volume receptors in the large veins and atria, thus suppressing ADH secretion
Where is oxytocin synthesized?
By paraventricular nucleus in the hypothalamus. It is stored and released by the posterior pituitary
What are the actions of oxytocin?
Contract of the uterus during childbirth at very low concentrations
Causes the ejection of milk from breast shortly after suckling (milk already produced by the breast alveolar cells)
Summarize hormonal function of lactation
Hypothalamus-decrease in release of dopamine= increase
-decrease in release of GnRH= decrease
Oxytocin stimulates contraction of the myoepithelisl basket cells produces milk ejection
Prolactin from anterior pituitary stimulates milk to synthesize by mammary aalveolar cells
How does uterine contractions stimulate lactation?
Uterine contraction causes stretch of cervix end of pregnancy
-oxytocin release causes contraction of myoepithelial cells
Suckling if lactating breast activates fear, pain, noise, fever for further oxytocin release
What are the hormones of the anterior pituitary hormones?
- Thyroid stimulating hormones (TSH)
- Adrenocorticotropic hormone (ACTH)
- Lutenizing hormone(LH)
- follicle stimulating hormone (FSH)
- Growth Hormone(GH)
- prolactin (PRL)
Explain control of secretion of Growth Hormone
GH secretion is pulsatile. The secretory pulses are much more likely to occur during the night in stages III & IV (non-REM) sleep than during the day
-secretion of GH requires the presence of normal plasma level of thyroid hormone
Note GH secretion is markedly reduced in hypothyroid individuals
Each of the promoters could act by increasing GHRH secretion, decreasing SST secretion of both
Most factors that stimulate growth hormone secretion, will also stimulate glucagon secretion.
Note Hence why these two hormones are part of the counter-regulator hormone to increase blood-glucose
The inhibitory effect of IGF-1 (somatomedin C) represents a negative feedback loop to the hypothalamus. IGF are made when GH act in target tissues e.g. liver
How does thyrotropin releasing hormone effect anterior pituitary release?
Increase thyrotrophs(10%) secretion of TSH
How does Corticotropin releasing hormone affect anterior pituitary Bohr,ones?
Increases corticotrophs (20-25%)
Secretes ACTH
How does GnRH affect anterior pituitary target hormones?
Increase gonadotrophs (10-15%) secretions- LH, FSH
High frequency pulses favor LH, low frequency pulses favor FSH
Also increases somatotrophs(50%)
Causes secretion of GH
The fact that eliminating hypothalamic input causes a decrease in growth hormone secretion indicates that GHRH is the main controlling factor
How does SST affect anterior pituitary gland secretion?
Somatotrophs(50%)
How does dopamine affect anterior pituitary gland secretions?
Decreases lactotrophs(10-15%)
Secretion: prolactin
When the connection between the hypothalamus and the anterior pituitary is severed (e.g., there is damage to the pituitary stalk), secretion of all anterior pituitary hormones decreases, except prolactin which increases. The secretion of prolactin increases because chronic source of inhibition (dopamine) has been removed
Explain the physiologic activity of growth hormone
- growth hormone is a major anabolic hormone and a stress hormone
- most of the direct actions of growth hormone are consistent with its action as a stress hormone
- A direct anabolic action of growth hormone is to increase the uptake of amino acids to promote protein synthesis
Note: most of the anabolic actions of growth hormones are indirect via growth factors, specifically IGF ( insulin like growth factors)
What are the direct catabolic effects of growth hormone(peptide hormone) ?
- Decreases uptake of glucose in fat and muscle which ra8ses blood glucose
- Mobilizes fats by increasing the activity of hormone sensitive lipase, therefore rais8ng free fatty acids
- In growth hormone deficiency, body fat increases
What are the direct anabolic effects (growth) of growth hormone(peptide)?
Increased uptake of amino acid into cells
What are the indirect anabolic effects (growth)?
Via IGF
What are the specific properties of the IGFs?
Circulates in the blood tightly to a large protein (whose production is also depending on growth hormone)
Note: increased half life and thus serves as a better 24 hour marker of GH. (Half-life of growth hormone is 15-20 mins)
- One of the major anabolic effects is to increase the synthesis of cartilage (chondrogenesis) in the epiphyseal growth plate in long bones, hence increasing bone length - IGFs also is hypothesized to increased lean body mass
Note: it could possibly explain why elderly individuals who have a decrease in growth hormone, have concomitant decrease in IGF and therefore a decrease in lean body mass
