Feb 13th Flashcards
General Mechanism of Hormonal Action
- Hypothalamic Neuroendocrine Cells release Hormone 1 into the blood vessels leading to the anterior pituitary.
- Anterior Pituitary Cells respond by secreting Hormone 2 into general circulation.
- Hormone 2 acts on:
Endocrine target tissues → Stimulates the release of Hormone 3.
Non-endocrine target tissues → Directly triggers physiological effects. - Hormone 3 (if released) enters general circulation and further regulates tissue responses.
- Tissue Response → Leads to the desired biological effect (e.g., metabolism, growth, stress response).
How is the pituitary gland connected to the hypothalamus?
Through the infundibulum (stalk).
What protects the pituitary gland?
Bone (sella turcica of the sphenoid bone).
What are the two parts of the pituitary gland?
- Anterior pituitary (adenohypophysis) – endocrine gland.
- Posterior pituitary (neurohypophysis) – extension of neural tissue.
What is the difference between the anterior and posterior pituitary?
- Anterior pituitary produces & releases hormones.
- Posterior pituitary stores & releases hormones made by the hypothalamus.
Dopamine (PIH – Prolactin Inhibiting Hormone)
Inhibits secretion of prolactin (PRL).
Prolactin Releasing Hormone (PRH)
Stimulates release of prolactin (PRL).
Thyrotropin-Releasing Hormone (TRH)
Stimulates secretion of thyroid-stimulating hormone (TSH) from the anterior pituitary.
Corticotropin-Releasing Hormone (CRH)
Regulates secretion of adrenocorticotropic hormone (ACTH), which influences cortisol production.
Somatostatin (GHIH – Growth Hormone Inhibiting Hormone)
Inhibits secretion of growth hormone (GH).
Growth Hormone-Releasing Hormone (GHRH)
Stimulates secretion of growth hormone (GH).
Gonadotropin-Releasing Hormone (GnRH)
Regulates secretion of luteinizing hormone (LH) & follicle-stimulating hormone (FSH), which control reproductive functions.
CRH
- in the Hypothalamic-anterior pituitary-adrenal
cortex axis - corticotropin releasing hormone (from the hypothalamus)
ACTH
-in the Hypothalamic-anterior pituitary-adrenal
cortex axis
-adrenocorticotropic hormone (from the anterior pituitary)
cortisol
- in the Hypothalamic-anterior pituitary-adrenal
cortex axis - glucocorticoid, chronic stress hormone
Where is CRH synthesized?
In the paraventricular nucleus (PVN) of the hypothalamus.
What stimulates CRH production?
Noradrenergic signaling, which increases pre-proCRH gene & protein expression.
How is CRH synthesized?
- Pre-proCRH gene → 196 AA precursor
- Processed to active CRH (41 AA)
- Released pulsatilely into circulation
What inhibits CRH release?
Cortisol (negative feedback loop) inhibits both CRH release & gene expression.
Where is CRH produced?
In the parvocellular neuroendocrine cells of the paraventricular nucleus (PVN) of the hypothalamus.
Where is CRH released?
At the median eminence into blood vessels of the hypothalamic-pituitary portal system.
What does CRH stimulate in the anterior pituitary?
Corticotropes, which secrete ACTH.
What is the main function of ACTH?
ACTH stimulates the adrenal cortex to produce cortisol, which regulates metabolism and the stress response.
What is ACTH derived from?
Pro-opiomelanocortin (POMC).
What does ACTH regulate?
The adrenal cortex, stimulating cortisol release.
What is the function of MSH?
Melanocyte-Stimulating Hormone (MSH) increases melanin production in response to UV radiation.
What does β-Endorphin do?
Acts as a natural painkiller in the CNS.
What is the role of enkephalin?
Plays a role in pain modulation, especially in fetuses.
What do MC3, MC4, and MC5 receptors regulate?
Hypothermia, hypotension, appetite, and feeding behavior.
what are convertases
- enzymes that cleave POMC
- different convertases give rise to different products
What are the two parts of the adrenal gland?
Adrenal cortex (outer) & adrenal medulla (inner).
What hormones are secreted by the adrenal cortex?
- Glucocorticoids (e.g., cortisol) – controlled by ACTH.
- Mineralocorticoids (e.g., aldosterone) – controlled by Renin-Angiotensin System (RAS).
- Sex steroids (e.g., testosterone in small amounts) – controlled by ACTH.
What hormones are secreted by the adrenal medulla?
Catecholamines (e.g., epinephrine & norepinephrine).
How is the adrenal medulla different from the adrenal cortex?
- The adrenal cortex secretes steroid hormones (regulated by ACTH & RAS).
- The adrenal medulla is a modified sympathetic ganglion that secretes catecholamines.
Why is cortisol essential for life?
It prevents hypoglycemia, regulates immune & inflammatory responses, and affects metabolism & brain function.
How does cortisol regulate blood sugar?
- Prevents hypoglycemia.
- Stimulates gluconeogenesis (glucose production in the liver).
What is cortisol’s role in the immune system?
- Suppresses the immune system.
- Regulates inflammation (used as an anti-inflammatory drug).
What tissues does cortisol break down?
- Skeletal muscle (for amino acids → gluconeogenesis).
- Bone (bone catabolism).
How does cortisol affect the brain?
Impacts mood, memory, and learning.
What is the difference between Cushing’s Syndrome & Cushing’s Disease?
- Cushing’s Syndrome → Excess cortisol (low ACTH).
- Cushing’s Disease → Excess ACTH from pituitary tumor (high ACTH).
What are the symptoms of Cushing’s Syndrome?
Hyperglycemia, hypertension, muscle weakness, obesity, moon face, depression, memory problems.
How is Cushing’s treated?
Surgery (remove tumor), medical management (BP, diabetes control).
What is Addison’s Disease?
Adrenal insufficiency → low cortisol levels.
What are the symptoms of Addison’s Disease?
Fatigue, muscle weakness, hypotension, hyperpigmentation, weight loss, salt cravings.
How is Addison’s Disease treated?
Lifelong corticosteroid replacement (hydrocortisone, fludrocortisone).
what is PPID
pituitary pars intermedia dysfunction
- affects older horses but has been diagnosed as young as 10
causes of PPID
- impaired pituitary
- leads to increased secretion of cortisol by adrenal glands
- results in high blood glucose & suppression of immune system
signs of PPID
- Hypertrichosis (excessive hair growth)
- Abnormal hair coat including patches
of long hair on legs, wavy hair on
neck, & changes in coat colour - Muscle atrophy
- Excessive sweating
- Formation of fat pads on top of neck,
tail head, & above/around eyes - Pot-bellied appearance
diagnosis and treatment of PPID
diagnosis: measure resting ACTH & fasting insulin
treatment: medication acts on pituitary glands to decrease circulating ACTH
- management: exercise, weight loss, limit sugar
Where is the thyroid gland located?
Below the larynx, on either side of the trachea, connected by an isthmus.
What is the largest purely endocrine gland?
Thyroid gland (20-25g).
How does the thyroid gland vary between species?
- Fibrous in cows & horses.
- Less distinct in dogs & cats.
Where is thyroglobulin made and stored?
Made by follicular cells, stored in the colloid.
What transports iodide into follicular cells?
Sodium-iodide transporter, then into the colloid by transporter called pendrin
What enzyme converts iodide (I⁻) into iodine (I₂)?
Thyroid peroxidase (TPO).
What is the difference between MIT & DIT?
MIT (Monoiodotyrosine) = 1 iodine attached.
DIT (Diiodotyrosine) = 2 iodines attached.
How are T3 and T4 formed?
- MIT + DIT = T3 (Triiodothyronine).
- DIT + DIT = T4 (Thyroxine).
How are T3 & T4 released into the bloodstream?
Thyroglobulin is taken up by follicular cells, cut by enzymes, and T3 & T4 are secreted upon TSH stimulation.
99% of thyroid hormones in blood circulation bound to plasma carrier protein are called:
thyroxin-binding globulin (TBG)
How do thyroid hormones travel in the blood?
Bound to carrier proteins (TBG, TTR, albumin).
Which form of thyroid hormone is biologically active?
Free (unbound) T3 & T4.
Why are thyroid hormones bound to carrier proteins?
- Prevents rapid clearance from blood.
- Provides a hormone reservoir.
- Regulates hormone availability to cells.
Thyroid Receptors Steps
- Thyroxine (T4) + protein
carrier - T4 → T3
(triiodothyronine) - T3 uses binding proteins
to enter nucleus - Hormone-receptor
complex binds DNA - hormone-receptor complex activates gene transcription
- New mRNA
- Protein
- Response
Regulation of TRH Secretion
- Pulsatile Secretion
- TRH is released in pulses, rather than continuously. - Age-Dependent Secretion
- Young animals secrete more TRH than older animals.
Thyroid activity declines with age. - Environmental Factors
- Stress & cold increase TRH secretion, stimulating thyroid hormone production to boost metabolism and energy. - Circadian Rhythm of Thyroid Hormones
- In humans, secretion peaks between 10 AM – 2 PM.
In rodents, secretion is highest at night (opposite to humans). - Effect on Metabolism
- Thyroid hormones increase basal metabolic rate (BMR)—the resting rate of caloric expenditure.
What is the main metabolic effect of thyroid hormones?
Elevate basal metabolic rate (BMR) & increase energy expenditure.
How do thyroid hormones affect reproduction?
Necessary for normal gonadal development & reproductive function.
Why are thyroid hormones crucial for fetal development?
Essential for brain & central nervous system (CNS) development.
What happens to thyroid hormone levels with age?
Thyroid hormone production declines.
Hypothyroidism
- abnormally low basal metabolic rate
- weight gain, lethargy, intolerance to cold
hyperthyroidism
- increased basal metabolic rate
- weight loss, muscular weakness, nervousness, protruding eyes
What is cretinism?
Congenital deficiency of thyroid hormones leading to impaired physical & brain development.
What are the two main causes of cretinism?
Maternal hypothyroidism & iodine deficiency.
How does iodine deficiency contribute to cretinism?
Iodine is essential for thyroid hormone production; deficiency prevents proper hormone synthesis.
What are the symptoms of cretinism?
Stunted growth, intellectual disability, speech/hearing impairment, delayed development.
How is cretinism treated?
Thyroxine (T4) replacement therapy, especially before 1 month of age.
When does thyroid hormone-dependent brain development begin?
Begins in utero and continues after birth.
What brain structures do thyroid hormones influence?
Dendrites, axons, myelin, synapses, & neuronal migration.
Why is myelin formation important?
Myelin speeds up nerve signal transmission and is essential for brain function.
How do thyroid hormones affect neuronal migration?
They help neurons reach the correct locations in the brain.
Where does the fetus get thyroid hormones before its thyroid develops?
From the mother’s thyroid hormones.
What is a goiter?
Abnormal enlargement of the thyroid gland, often due to iodine deficiency.
What causes goiters in hypothyroidism?
Low iodine → Low T3/T4 → Increased TRH → Increased TSH → Thyroid growth.
What is the role of iodine in thyroid function?
Iodine is required to make thyroid hormones (T3 & T4).
Graves disease due to hyperthyroidism
- Autoimmune antibodies activate thyroid gland, leading to high plasma T3 and T4
- high thyroid hormone concentration leads to low TRH, & subsequently low plasma TSH
- exophthalmia
thyroid disorder treatments
- Surgery (hemithyroidectomy)
- Hormone supplementation (start with low dose)
- Radiation therapy (cancer)
- Blockers (thiouracil derivatives & thiocarbamides decrease
iodination & conversion from T4 to T3) - Stimulants (e.g. furosemide increases conversion from T4 to T3)
- Diet, electrolyte infusions, etc.
What is the most common cause of hypothyroidism in dogs?
Primary hypothyroidism (thyroid destruction).
What are the two main causes of primary hypothyroidism?
Lymphocytic thyroiditis & idiopathic thyroid atrophy.
Which dog breeds are predisposed to hypothyroidism?
Doberman Pinscher, Golden Retriever, Irish Setter, Miniature Schnauzer, Dachshund, Cocker Spaniel, Airedale Terrier.
What is secondary hypothyroidism?
Hypothyroidism caused by lack of TSH or thyroid destruction due to cancer.
How much thyroid function must be lost before clinical signs appear?
At least 75% of thyroid tissue must be non-functional.
