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What are the thyroid hormones?
T3 and T4 (thyroxine)
How does TSH interact with follicular cells?
TSH binds to receptors on the basal surface of follicular epithelium cells
How is TGB synthesized/secreted?
- Thyroglobulin synthesis occurs in the RER and then modification occurs in the RER and Golgi.
- Vesicles containing TGB are transported from the trans Golgi network to the apical plasma membrane of follicular cells where they are released into the colloid.
How is iodine incorporated into TGB?
- Iodine ions are actively transported from the bloodstream by symporters on the basal surface of follicular cells.
- Iodine is transferred to the apical surface of the cells where it is covalently linked to tyrosine residues on TGB just as TGB is released into the colloid.
- The linkage is carried out by thyroid peroxidase - located in follicular cell membrane.
How are T3 and T4 formed?
A single iodination of one TGB tyrosin residue results in the formation of monoiodinated tyrosine (MIT) whereas two iodinations results in diiodinated tyrosine (DIT). The coupling of one MIT and one DIT results in the formation of triiodothyronine (T3) while coupling of two DIT's results in tetraiodothyronine (T4).
How is thyroid hormone released?
- Stimulated by TSH which stimulated endocytosis of iodinated TGB into follicular cells
- Endocytic vesicles fuse with endosomes,and the iodinated TGB is digested by proteolytic enymes which generates free T3 and T4
- T3 and T4 are released at the basal plasma membrane of the follicular cells where they enter T3/T4 enter the connective tissue spaces of the thyroid gland and then pass through pores in fenestrated capillaries to enter the bloodstream
Which of T3/T4 is released more often from follicular cells, and why is this beneficial?
- T4- 90% of thyroid hormone released is T4
- T4 has a greater affinity for thyroxine-binding globulin (TBG) - the plasma carrier protein
How does thyroid hormone affect target cells?
- Free T3 and T4 within cells can bind thyroid hormone receptors within target cells and thus affect gene transcription.
- T3 has a higher affinity for these receptors (which explains its higher biological activity)
- Target cells can readily convert T4 to T3
How is thyroid hormone regulated?
- The thyroid axis is regulated by negative feedback. Increased levels of T3/T4 signal to the PVN to inhibit further production of T3/T4 by suppressing TSH release.
- Insufficient feedback (deficient iodine, decreased T3/T4 release) results in an abnormal enlargement of the thyroid gland (goiter) due to excessive secretion of TSH which contstantly stimulates the follicular cells
Compare the histology of follicular and parafollicular cells.
- Follicular: tall, cuboidal, contain colloid droplets, have microvilli for colloid recapture
- Parafollicular: squamous, many secretory granules (peptide)
What are six functions of thyroid hormone?
- oxygen consumption/utilization
- responses to adrenaline
- Na/K channel openings
- Heart and respiratory rate
- lipid/carbohydrate metabolism
- Growth, reproduction, and development
What is hyperthyroidism?
- auto-immune disease
- occurss independent of the PVN (TRH) and pituitary (TSH)
- Immune system generates a molecule that mimics the stimulatory action of TSH on TH synthesis and release
- Can develop a goiter
What are the two major components of the adrenal gland and their developmental origins?
- Cortex (outer portion)- mesodermally derived
- Medulla (inner portion)- neuroectoderm derived
Describe the structure of the cortex of the adrenal gland.
Divided into zones whose cells express different enzymes that modify cholesterol to produce different steroid hormones- Zona Reticularis, Zona Fasciculata, and Zona Glomerulosa
What is the zona reticularis?
clusters of of cells on inner aspect of adrenal cortex, produce and secrete weak androgens (eg. DHEA- dehydroepiandrosterone)
What is the zona fasciculata?
Tall columns of cells in central aspect of adrenal cortex, produce and secrete glucocorticoids (eg. cortisol) under the control of ACTH from the anterior pituitary
What is the zona glomerulosa?
small, spherical nests of cells in the outer portion of the adrenal cortex, produce and secrete mineralocorticoids (eg. aldosterone; stimulated by angiotensin II generated, in part, in kidney)
How is the adrenal axis regulated?
The hypothalamic/pituitary/adrenal axis is regulated by negative feedback. Increased levels of cortisol signal the PVN to inhibit CRH production, which, in turn, decreases ACTH production by the anterior pituitary.
Describe the structure of the medulla of the adrenal gland.
- Contains chromaffin cells, which are modified postganglionic sympathetic neurosecretory cells that lack dendrites and axons; Stimulated by preganglionic sympathetic nerves which travel to the adrenal medulla without first synapsing in a peripheral ganglion
- Cells of the medulla produce catecholamine hormones (eg. epinephrine)
- Catecholamines are secreted in response to stimulation by preganglionic sympathetic nerves.
What are some important histological features of cortical cells in the adrenal gland?
The cortical region stores cholesterol and steroids in prominent lipid droplets.Steroid hormone synthesis, which begins as cholesterol, occurs via enzymes found in both mitochondria and smooth ER which are often in close proximity. As a result steroid secreting cells like those of the adrenal cortex and those that we will see in the ovary and testis have prominent smooth ER and the mitochondria3and many ER junctions (lipid transfer proteins help move the steroid precursorsbetween these two compartments where the enzymes are located that modify them).
What is an important histological feature of mitochondria in the adrenal gland?
The christae of mitochondria have characteristic tubulo-vesicular shapes which are an excellent diagnostic on transmission electron micrographs.
What are some important histological features of Chromaffin cells in the adrenal medulla?
Chromaffin cells of the adrenal medulla synthesize and secrete amines that are stored in classical membrane-bound secretory vesicles/granules that undergo exocytosis when stimulated by pre-ganglionic sympathetic neurons that enter the adrenal medulla.