Endocrine pathophysiology: hypothalamus, pituitary, thyroid and adrenal Flashcards
Which hormones does the anterior pituitary secrete?
Anterior pituitary secretes:
* Growth hormone
* Follicle stimulating hormone
* Luteinizing hormone
* Adrenocorticotrophic hormone
* Thyroid stimulating hormone
* Prolactin
Which peptide hormones does the posterior pituitary secrete?
Posterior pituitary secretes:
* Oxytocin
* Vasopressin (antidiuretic hormone)
Neurones send axons down from the ______________
Neurones send axons down from the hypothalamus
The anterior pituitary is ectodermal in origin, why is this significant?
The anterior pituitary is ectodermal in origin, this is significant because it connects the anterior pituitary’s functions with the nervous and endocrine systems. It highlights the relationship these systems have to regulate processes/
How is the hypothalamus connected to the anterior pituitary?
The hypothalamus is connected to the anterior pituitary by the hypothalamic-pituitary portal system (blood vessels)
How does the hypothalamus regulate the anterior pituitary?
The hypothalamus regulates the anterior pituitary by releasing trophic hormones into the blood vessels that travel to the infundibulum to the anterior pituitary. These trophic hormones stimulate or inhibit the release of hormones from endocrine cells of the anterior pituitary.
Antidiuretic hormone (vasopressin)
Antidiuretic hormone (ADH) (vasopressin):
* synthesised in the paraventricular nucleus (part of hypothalamus) and transported down the nerves in secretory vesicles before being released (exocytosis) under the influence of an appropriate stimulus
* Anti-diuretic hormone acts to maintain blood pressure, blood volume and tissue water content by controlling the amount of water and hence the concentration of urine excreted by the kidney
Oxytocin
Oxytocin:
* synthesised in supraoptic nucleus (hypothalamus)
* involved in stimulating the uterus during parturition and ‘milk let-down’ in breasts
The thyroid
Thyroid:
* largest endocrine gland in human body, situated in front of neck.
* regulated by the hypothalamus & anterior pituitary
* mandatory for body temperature, regulation, basal metabolic rate, metabolism, growth, reproductive system, etc.
* Secretes three hormones: Calcitonin, important in calcium homeostasis.
Triiodothyronine (T3) and thyroxine (T4), important in growth and metabolic function.
What happens if there is an issue with the thyroid or its hormones?
If there is is an issue with the thyroid or its hormones:
* In absence of thyroid, hypothyroidism occurs.
* If hormones are deficient at birth, congenital abnormality occurs. Cretinism appears in children.
* Thyroid hormones, if deficient, are replaced at birth to avoid mental and growth retardation.
* If there is too much thyroid hormone, hyperthyroidisim occurs.
What is the thyroid composed of?
The thyroid is composed of large number of follicles filled with coli. Major constituent glycoprotein is thyroglobulin, secreted by the cells into coli.
The posterior pituitary has a neuronal developmental origin as a down-growth from diencephalon, why is this significant?
The posterior pituitary has a neuronal developmental origin as a down-growth from diencephalon. This is significant because the origin emphasizes the integration of neural and endocrine signalling.
Where is thyroid hormone secreted from?
Thyroid hormone is secreted from the follicular cells
How are thyroid hormones synthesized?
Thyroid hormone synthesis:
* Thyroid follicular cells take up iodide
– oxidize iodide to Iodine via hydroperoxidase
– covalently attach the iodine to the tyrosines of thyroglobulin within the lumen of the follicle
Thyroid epithelial cells are organized into _________ that secrete thyroglobulin
(large glycoprotein, mw 660Kd) and accumulates in the follicles as “__________________”
Thyroid epithelial cells are organized into follicles that secrete thyroglobulin
(large glycoprotein, mw 660Kd) and accumulates in the follicles as “colloid”
What happens when the thyroid is stimulated by TSH?
- On stimulation by TSH (from the anterior pituitary)
- Iodide is actively transported from the blood by the iodide pump, transport driven by electrochemical gradient.
- Iodide transported into the colloid of the follicular luman by a second transporter.
- Iodide interacts with accessible tyrosine residues of thyroglobulin.
- Intermediates MIT and DIT are formed
- Coupling of MIT and DIT produce T4 (x2 DIT) and T3 (x1 MIT and x1 DIT)
– follicular cells endocytose the iodinated thyroglobulin
– break it down in lysosomes
– release the iodinated tyrosine derivatives as tetra- iodothyronine (thyroxine) (T4) or triiodothyronine (T3)
What is total T4 level decreased in?
Total T4 level is decreased in:
* Premature infants
* Hypopituitarism
* Nephrotic syndrome
* Liver cirrhosis
* Starvation & severe protein energy malnutrition (PEM)
* Protein losing entropathy
Facts about Thyroid hormones
Thyroid hormones:
* Lipophillic allows them to bind to blood serum proteins
* T4 less active than T3
* 99% of T3 and T4 are bound to plasma proteins (thyroid-binding globulin).
* 0.04% T4 and 0.4% T3 occur in free form (can enter target cells).
* They are excreted in the bile and urine.
* T4 has a half-life of 6-7 days; T3 has a half-life of 1-2 days.
* Oral absorption of T4 is 80% and T3 95%
* Readily absorbed from GIT and excreted in bile and urine.
* Some of the circulating T4 is deiodinated to T3, the more potent and rapidly acting form.
* 5:1 is the ratio of T4:T3 in thyroid.
* Thyroxine needs selenium and iodine> T3
* Iodine is required for synthesis
Dietary sources of iodine
Dietary sources of iodine
* Iodized table salt
* dairy products,
* fish
Iodine adult requirement?
Iodine adult requirement: 150 mg, increased to 200 mg in pregnancy.
Role of Iodine in T4 and T3 formation
- Oxidation in cells by peroxidase enzyme
- Organification –binding of iodide with tyrosine in thyroid leading to formation of monoiodotyrosine and diiodotyrosine.
- Coupling of MIT and DIT to form T4 and T3, which are stored in gland. When required, released in blood by proteolysis.
*
How do thyroid hormones regulate body temperature?
What other effects do they have?
Thermogenesis: thyroid hormones **regulate body temperature in humans
uncouple ATP synthesis from metabolism
by increasing expression of uncoupling protein (UCP) : generates heat
*direct effect on mitochondria in brown adipose tissue and skeletal muscle
*may be most important role of T3/4 in humans
* increase glucose absorption in GI tract
* enhance lipolysis glycogenolysis and gluconeogenesis
* increased metabolism increases temp
* increase adrenoreceptor expression> potentiate adrenaline and noradrenaline response
Central effect: new evidence that T3/4 act at hypothalamus to:
*stimulate sympathetic output to brown fat (thermogenesis) and liver (gluconeogenesis)
*increase food intake
*regulate body weight (including seasonal changes)
When stimulated to release ____________ ___________, follicular cells endocytose a portion of the colloid containing the iodinated thyroglobulin. Through the action of proteolytic enzymes within these cells, the thyroid hormones are released from the thyroidglobulin structure and actively transported in the blood.
When stimulated to release thyroid hormones, follicular cells endocytose a portion of the colloid containing the iodinated thyroglobulin. Through the action of proteolytic enzymes within these cells, the thyroid hormones are released from the thyroidglobulin structure and actively transported in the blood.
How is thyroid hormone secretion regulated?
Thyroid hormone secretion is regulated by:
Thyroid stimulating hormone
Thyroid stimulating hormone is regulated by thryotrophin releasing hormone
Thyroid stimulating hormone secretion is inhibited by somatostatin.
Iodide consumption
