Endocrinology Flashcards
7 hormone facts
More than one produced in one endocrine gland
More then one tissue secrets the same hormone
More than one target cell type for a signal hormone
A single target cell can be influenced by more than one hormone
Secretion varies over time and will be effected by changes in the environment
Hormones can be blood borne or neuronally driven
Some hormones are excreted from tissues that have other functions
Synthesis and secretion post translational modification of peptide hormones
1) peptide cleavage
2) glycosylation
3) phosphorylation
4) sulfation
5) amidation
6) acetylation
7) subunit aggregation
Describe hormone release feedback control
This is predominantly negative
But can also be positive
Ie) output counteracts input and is frequently seen in the trophic hormones
Hormone release neuroendocrine reflexes
Combination of neural and hormonal processes
Not the same as neuromodulation
Hormone release rhythms
Release of hormones is entrained to environmental cycles which vary in interval length and duration
Melatonin secretion peaks at night
Cortisol secretion has two predominant phases
Explain carrier proteins with hormone delivery
Carrier proteins can be general or specific to the hormone in question dictated by binding affinity
Specific carries - corticosteroid binding globulin to corticosteroids thyroid hormone binding globulin and transthyretin to thyroid hormones
General carrier - albumin
Hormone activation
Metabolism of the precursor or release from the carrier protein will activate the hormone that will then have a half life in the blood
The length of time for hormone half life follows the general pattern
1) single amino acid derivatives = minutes
2) peptide hormones = mins to hours
3) steroid hormones = hours
Hormone inactivation
Enzyme degradation
Hormone receptor complex endocytosis
Conjugation
Endocrine dysfunction types
Hyposecretion
Hypersecretion
Target cell
Describe hyposecretion of endocrine dysfunction
Primary or secondary usually the result of atrophy of the endocrine gland and normally treated through replacement therapy
Describe hypersecretion of endocrine dysfunction
Primary or secondary usually the result of a benign tumour (adenoma) normally treated through inhibition or removal
Describe target cell endocrine dysfunction
Lack of receptors or biomechanics machinery at the target cell
Ie) hyperinsulinemia
Target cell responsiveness is also altered naturally
Response at target cell
Up and down regulation
Permissiveness
Synergism
Antagonism
Up and down regulation response at target cells
Receptors at the target cell are themselves regulated in response to hormone levels influencing abundance and affinity
Measurement of binding kinetics for hormone/receptor complexes relies heavily on the
Chemical law of mass action
Do all hormone receptor complexes adhere to the law of mass action
Non-cooperative = law of mass action is upheld
Positively cooperative = ligand binding increases receptor affinity of vacant receptors
Negatively cooperative = ligand binding decreases receptor affinity of vacant receptors
Permissiveness response at target cell
One hormone cannot fully exert its effect without the other being present
Synergism response at target cell
The combined effect is greater then the sum of the parts
Antagonism response at target cells
The actions of one hormone reduces the effectiveness of the second can be direct or indirect
What are the two types of hormone receptors
Membrane bound
Nuclear receptors
Membrane bound hormone receptors
Ligand gated
Enzyme linked
Guanylyl cyclase and G protein linked receptors
Second messenger system includes
- adenylate cyclase
- guanylate cyclase
- inositol phosphate and diacyl glycerol
Nuclear receptors
Most lipophilic hormones act through nuclear receptors and many genes will have responsive elements
Nomenclature of
Anterior pituitary
Posterior pituitary
Pars distalis
Adenohypophysis
Pars nervosa
Neurohypophysis
The hypothalamus and posterior pituitary form a
neuroendocine system with cell bodies based in the hypothalamus
Posterior pituitary hormones are synthesized in the
Hypothalamus
Cell bodies then extend down the ___ and terminate in the ____
Infundibulum and terminate in the posterior pituitary
Describe neurohypophysial peptides
Two nonapeptides = OT and AVP
Precursor peptides produced in the hypothalamus - neurophysins
Closely related but one can work within the other
AVP and OT neurophysins + proteolytic enzymes are packages in ___ and begun to migrate down the axon to the ___ where the nerve terminals are located
Secretory Granules
Neurohypophysis
Vasopressin, arginine vasopressin, and antidiuretic hormone release and action
Release
- reduced ECFV which increases plasma osmolaitiy which increases osmorecpetor activity which increases vasopressin release
Action
- increases h2o reabsorption in renal tubules
- vasoconstriction of vascular smooth muscles
Oxytocin release and action
Release
- birth canal distension increases oxytocin release
- infant suckling increases oxytocin release
Action
- increases utrine muscle contraction during parturition
- increases milk ejection from breast
Describe behavioural aspects of OT
Increases maternal behaviour in rats but estrogens need to be present
Plasma OT levels increase during sexual arousal in both sexes
Act as neuromodulators in the brain to influence social recognition memory and affiliative behaviours such as paid bonding
Describe behavioural aspects of AVP
Stimulates release of ACTH that is synergistic with CRH
Seems to play a greater role in males rather then females in regard to social recognition and consolidation of social memory
Aggression courtship scent marking and learning
Adenohypophysial cells
Histological and cytological methods have provided definitive evidence on the cellular source for each hormone release from the adenohypophysis
Hypothalamic anterior pituitary axis
Hormones synthesized and release from the anterior pituitary are under control of the hypophysiotropic hormones that can be stimulatory or inhibitory
What are the hormones of the glycoprotein family
Follicle stimulating hormone
Leutinizing hormone
Thyroid stimulating hormone
Human chorionic gonadotropin
Each has a A and B subunit the amino acid sequence of the A subunit is similar but the B subunit varies
Explain pars intermedia
Many animals have an anatomically separate pars intermedia
The predominant endocrine product is alphaMSH
In humans this is also the case during development
As adults these cells are not anatomically distinct but still synthesize and secrete aMSH
Normal growth means
1) Protein, Fat, Cartilage synthesis
2) cell proliferation
3) bone lengthening
Normal growth is influenced by
1) generic resolve
2) diet and nutrient transfer
3) disease and stress
4) multiple layers of hormonal control
Growth rate
GH levels increase during puberty
In makes testicular androgens are v. Important and increase dramatically during puberty
Adrenal androgens also increase and may be more important in females
Testosterone and estrogen both ultimately put brakes on
Growth hormone (GH) production and inhibition
Production stimulated by GHRH
Inhibited by GHIH
What is the most abundant adenohypophysial hormone
Growth hormone
Spontaneous secretion of GH over a 24 hour period usually peaks when
In the first 90 mins of sleep
The somatomedin hypothesis
Growth hormone does not have a direct effect on growth of any given tissue but rather acts indirectly through somatomedins
Somatomedins hypothesis
There are two main somatomedins
Insulin like growth factors 1 and 2
They are 70 and 67 amino acids respectively and share many similarities with insulin
IgF 2 is more abundant in adults
Circulating levels of IGF 1 increase massively during ___ but ____ increases moderately by comparison
Pubertal growth spurt
GH
The __ is the mature bone shaft with the ___ at either end
Diaphysis
Epiphysis
In a growing bone the ___ is separated from the ___ by the ___
Epiphysial
Diaphysis
Epiphysial plate
___ produce enzymes collagen and proteins to provide framework for hydroxyapatite crystals. They deposit new bone on the outer edges of old bone to increase width
Osteoblasts
Osteoblasts will ultimately turn into mature bone cells ___
Osteocytes
Bone length grow is regulated by cartilage cells ___ located in the epiphyseal plates
Chondrocytes
Thyroid hormones are
Involved in energy homeostasis
Hypothyroidism = reduced growth TH is largely permissive
Insulin is involved in
Carbohydrate metabolism
Deficiency can block growth and excess can promote growth potential cross reactivity with IGF receptors
Androgens and estrogens arrest
Long bone length increase by closure of the epiphyseal plate
Prolactin belongs to the ___ family and influenced
GH
Mammary gland growth as well as aspects of the immune system
Placental lactogen belongs to the __ family and influences
GH
Neonatal development maternal glucose and amino acid supply
Peaks around mid pregnancy until full term
Neurotrophic factors are
Nerve growth factors
Erythropoietin are
Red blood cell growth factor
Platelet derived growth factors are
Vascular injury repair but also involved in the development of artherosclerosis
Epidermal growth factors enhanced proliferation of
Epidermis
Gut lining
Pulmonary lining
Tumour derived growth factors angiogenesis
Fibroblast growth factors
Transforming growth factors
Why regulate calcium
Calcium is perhaps the most tightly regulated ion in circulation
- 99% of the bodies calcium is calcified structures
- 0.9% is intracellular
- 0.1% exists in the ECF half is bound to proteins or negatively charged ions and the rest is free from Ca2
Cell-cell integrity of tight junctions
Cofactor for clotting blood
Required for structural form of bone and teeth
Neuromuscular excitability
Reduced calcium leads to tetanic muscle contraction and high levels lead to reduced muscular contraction
Stimulus secretion coupling (calcium importance)
Many cells willl require calcium to enter the cell to stimulate the secretion of a given substance
Regulation of calcium ____ impacts phosphate concentrations
ALWAYS
Bone remodelling requires deposition and resorption using
Osteocytes =
Osteoblasts =
Osteoblasts =
Osteocytes = mature bone cells
Osteoblasts = bone builders responsible for depositing the collagen matrix
Osteoclasts = bone breakers
Hormones involved in calcium regulation
Parathyroid hormone
Vitamin D3
Calcitonin
Describe parathyroid hormone
Negative relationship between plasma concentration and plasma (Ca2) that is extremely sensitive
Vitamin D3 (cholecalciferol) describe
Needs to be converted to 1,25-OH2)-vitamin D3 (calcritol)
Calcitonin is
The only hyocalcaemic hormone
Parathyroid hormone and bone
1) fast homeostatic regulation of Ca from bone fluid space
2) slower balancing of total body calcium from resorptive processes
What does parathyroid hormone do for the kidneys
PTH increases and decreases phosphate reabsorption
What does parathyroid hormone do for the intestine
Actions are indirect through stimulation of vitamin D3 production
Why is vitamin D considered a hormone
Because it can be produced in the skin from 7-dehydrocholesterol
Two important enzymatic steps that involve the sequential addition of hydroxyl groups
1) activation of 1alpha hydroxylase is the most important step and this enzyme is regulated by PTH
Target sites for vitamin D3
The gut is the best documented area of vitamin D3 action
Where both fast and slow components are initiated
Explain calcitonin
Not involved in day to day regulation but may be involved during the absorptive state and also during pregnancy
Calcitonin has both hypocalccaemic and hypophosphatemic effects
For the most part bone resorption and bone disposition balance each other out but
There are times when this is not the case
Osteoblasts are derived from ____
Osteoclasts are derived from___
Stromal cells in the bone marrow
Macrophages in the bone marrow
Osteoblasts and its precursor cells produce two main messengers __
RANKL (receptor activator of NFkB ligand)
Osteoprotegerin
Estradiol stimulates the production of
Osteoprotegerin
Osteoporosis is
Reduced bone mineral density
Prevalent in pre and post menopausal woman
Onset of osteoporosis and about 1% of bone mass is lost every year
Osteoporosis therapy
Exercise
Ca supplements
HRT
Calcitonin
SERMS and ANGELS
Tetraiodothyronine (T4) and triiodothyronine (T3) are both derived from _____ and synthesized in the ___ of the thyroid gland
Thyroglogulin
Follicular cells and the colloid of the thyroid gland
T4 and T3 are collectively referred to as the ___ hormones and are involved in the regulation of ____ and are key during ___
Thyroid hormones
Regulation of metabolic rate
Key during development
What are thyroid hormones basic ingredients
The amino acid tyrosine and the element iodine
Tyrosine can be made in the body whereas iodine is an essential component of our diet
Thyroid hormone deiodination
Deiodinases can have a strong preference for specific THs
Type 1 has a strong preference for reverse T3
Type 2 deiodinates only the outer ring
Type 3 deiodinates only the inner ring
These enzymes can be tissue specific
Actions of thyroid hormone
Calorigenic
TH is the most important regulator of basal metabolic rate
Actions of thyroid hormone
Sympathomimetic effect
Action is similar to the sympathetic nervous system
Increases target response to catecholamines
Actions of thyroid hormones
Cardiovascular
Largely as a result of the increase in catecholamine receptors and calorigenic effects
Actions of thyroid hormones
growth
Synergistic actions with both GH and IGFs
TH is essential for normal growth and neural development
Thyroid hormone abnormalities
This is one of the most common endocrine disorders and is very prevalent in young adult women
Includes both hypothyroidism and hyperthyroidism either of which are characterized by goiter
Goiter is
An over stimulation of the thyroid gland and not necessarily related to the capacity of the gland to synthesize and release TH
Exophthalmos is a thyroid hormone abnormality that is
A common feature of Graves’ disease which is an autoimmune disease
Melatonin is
The primary hormone released from the pineal gland and is synthesized from the amino acid tryptophan
Melatonin is synthesized and released in a rhythmical fashion that is closely related to ____
Circadian rhythms
Scotophase = dark
Photophase = light
Darkness is a universal stimulus for the synthesis and release of ___ from the ___ suggesting a strong link between the pineal and the optic tract
Melatonin
Pineal gland
The melatonin link comes in the form of the _____ which is our major biological clock
Suprachiasmatic nucleus (SCN)
Our major biological clock is where the ____
Interaction between PER genes and CLOCK proteins cycle at a remarkably constant rate that shifts depending on light cues
Melatonin release peaks in humans usually __
In the middle of the night
___ involved in melatonin synthesis also follows a rhythm
Enzymes
___ follows cycles so there is a link between melatonin and ____ hormones and ___
Reproduction
Sex
Reproduction
Adrenal hormones
Mineralocorticoids
Glucocorticoids
Sex hormones
Epinephrine
Norepinephrine
What are the adrenal steroids released from the adrenal cortex
Mineralocorticoids = aldosterone
Glucocorticoids = cortisol
Sex hormones = dehydroepiandrosterone and androstenedione (androgens) and estrogens
Catecholamines released from the adrenal medulla
Epinephrine - about 80%
Norepinephrine - about 20%
Cholesterol as a precursor three main parent molecules
C21- pregnane
C19- androstane
C18- estrane
Mineralocorticoids:
Aldosterone acts on distal and collecting tubules of the ____ in the ___
Nephron
Kidney
Mineralocorticoids regulates ____ which has implications on the ___ and the ___ systems
Body fluid volume
Renal
Cardiovascular
Mineralocorticoids steroid is essential for life it promotes ___ retention and ___ excretion in the kidney
Na
K
Secretion of mineralocorticoids is regulated by the ____ system and also directly by circulating __ concentrations
Renin angiotensin system
K
Aldosterone regulation is largely independent of the ___
Pituitary gland
Hyperaldosteronism can be either ___ or ___ symptoms present as hypernatremia hypokalemia and usually hypertension
Primary (Conns syndrome)
Secondary
The adrenal gland produces small amounts of both male and female sex steroids as ____ in an ____
DHEA
Adrenal androgen
Why are estrogens considered female sec steroids and androgens considered male sex steroids
In males testosterone overpowers the actions of DHEA however as females otherwise lack androgens DHEA plays a role in the pubertal growth spurt hair growth and the female sex drive
Adrenogenital syndrome
Symptoms are dependent on sex and age of hyperactivity onset
Adult females - masculinity, fascial hair deepening of voice ect.
Newborn females - pseudohermaphroditism
Adult males - no effect
Pubertal males - precocious pseudopuberty
Glucocorticoids direct actions
Stimulates gluconeogenesis
- generation of glucose from non carbohydrate substrates (amino acids pyruvates and glycerol)
Inhibits glucose uptake by many peripheral tissues
Stimulates protein degradation in muscle
Stimulates lipolysis mobilising fatty acids as an alternative energy source
Glucocorticoids permissive actions
Vascular collapse during stressful events in the absence of glucocorticoids
Glucocorticoids anti-inflammatory and immunosuppressive
This anti inflammatory effects are seen following administration of supra physiologic or pharmacologic levels
Prevention of leucocytes infiltration into the wound site
Atrophy of lymphatic system
Cortisol hyper/hypo secretion issues
Cushing’s syndrome (hyper)
Addison’s disease (hypo)
Cushing’s syndrome
Hypersecretion
Increased amounts of CRH or ACTH
Adrenal tumours
Ectopic ACTH release
Symptoms
- excess glucose, fat deposition in the face and abdomen thin legs and arms and facial hair excess
Addison’s disease
Hyposecretion
General name for bilateral damage to the adrenals
Can also be primary or secondary in nature
Symptoms
- increased integument pigmentation, weakness, weight loss, hypotension, salt craving and hypoglycaemia
General adaptation to stress
1) primary alarm response
2) secondary resistance response
3) tertiary exhaustion response
Describe primary alarm response for the adaptation to stress
Catecholamine surge into the system
Increase BMR
Increase Blood flow to required organs
Hepatic glycogenolysis
Secondary resistance response to Stress
Described actions of cortisol on metabolism
Continued mobilisation of glucose for central organs
Continued breakdown of alternative energy stores (lipids and proteins)
Tertiary exhaustion response to stress
Muscle wasting, hyperglycaemia (diabetes)
Atrophy of the immune system gastric ulcers
Vascular derangements
The adrenal medulla essentially acts as an extension of the ____
Sympathetic nervous system
Catecholamine release from the adrenal medulla is largely under the control of the ___
SNS
Both catecholamines are stored in ____
Chromaffin granules
Epinephrine and norepinephrine are both the active Ligands in the ____ system and they will bind to one of the 4 ____ receptors (which are)
Adrenergic system
Adrenergic receptors
Alpha 1,2 beta 1,2
Describe epinephrine
Rapid mobilisation of the bodies energy reserves
Increase cardiac output and total peripheral resistance
Increase coronary and skeletal muscle arteriolar dilation
Reduce gut motility
Increases glycogenolysis in liver and muscle
Increased CNS alertness
Dilates pupils and flattens theblens
Increases sweating
