Question

The results of Felix’s thyroid function labs indicate that he has hypothyroidism.
(a) Discuss the normal negative feedback loop that regulates thyroid hormone release, starting with the hypothalamus.

(b) Briefly describe how the thyroid gland responds to TSH.

(c) Suppose that Felix’s levels of TSH and T4 were both abnormally low. Considering the normal negative feedback loop regulating the thyroid gland, explain how these lab results are possible.

Answer 1

a)

The thyroid hormones (thyroxine and triiodothyronine ("T4 and T3")) synthesized by thyroid glands control metabolism all over the body. Negative feedback loop is extensively used to regulate secretion of thyroid hormone

• From hypothalamus thyroid releasing hormone (TRH) is secreted. TRH stimulates cells in anterior pituitary gland to synthesize and secrete thyroid-stimulating hormone (TSH).
• TSH binds to cells in the thyroid gland and stimulates synthesis of thyroid hormones

c) Felix’s TSH level and T4 levels are abnormally low. The most possible reason could be the un-ability of anterior pituitary gland to respond to the TRH. So TSH is not made and since TSH is absent , thyroid gland is not activated to produce T4. So the level of TSH and T4 is less in blood.

Now the levels of thyroid hormones are increased in the blood. When these levels reach beyond a certain threshold, TRH secretion from hypothalamus is inhibited. Here the thyroid level is giving feedback signal to stop production. This is an example of "negative feedback".

When TRH secretion is inhibited, the stimulation of pituitary gland is inhibited and this leads to the shut-off of TSH secretion, and eventually thyroid hormone secretion.

When the concentration of thyroid hormone levels fall below the threshold, entire loop starts again.

b)

TSH is a cysteine-knot growth factor super family member. It is a dimer comprising one alpha and one beta subunit linked by non-covalent bonds. Alpha subunit TSH is similar to luteinizing hormone (LH) and follicle stimulating hormone (FSH), but have different beta subunits. TSHB gene encodes beta subunits.

TSH give signal to cells through cognate receptor, thyrotropin receptor or TSHR. These are usually found on the cell surface of the thyroid follicular cells. TSH receptor belongs to the G protein-coupled receptor superfamily of integral membrane proteins. TSH receptor also has 2 subunits, a large ectodomain (alpha) and a small ectodomain (beta), these subunits interact with G proteins to initiate signaling.

When TSH is bound with TSHR on thyroid epithelial cells it stimulates production of iodine transporter, thyroglobulin, and thyroid peroxidase proteins. These are very essential for the synthesis and secretion of thyroid hormones.