Thyrotropin-Releasing Hormone (Protirelin, TRH)

• Overview: thyrotropin-releasing hormone, TRH

  • Tripeptide

  • Location: hypothalamus (and other brain regions)

  • TRH:   portal venous system:   pituitary stimulation :  thyroid-stimulating hormone (TSH, thyrotropic) production :  thyroid-stimulation and release :   thyroxine (T4) and triiodothyronine

  • TRH stimulation of thyrotropin:

    • Blocked by thyroxine

    • Enhanced by thyroxine deficiency

• Chemistry/pharmacokinetics: TRH

  • Glu-His-Pro-NH₂

  • IV administration

  • Plasma half-life: 4-5 minutes

• Pharmacodynamics:  TRH

  • Hyperthyroidism: serum thyrotropin level reduced

  • Primary hypothyroidism:

    • Thyrotropin levels: high

    • Enhanced thyrotropin response to TRH

  • Secondary (pituitary) hypothyroidism:

    • Thyrotropin serum levels: low (by sensitive TSH assay) or "inappropriately normal"

    • TSH often does not increase after TRH

  • Tertiary (hypothalamic) hypothyroidism:

    • Serum thyrotropin levels: normal or low

    • Thyrotropin response to TRH: normal or attenuated

  • TRH infusion:

    • Increased prolactin released by the pituitary

    • No effect on growth hormone or ACTH

    •  Pituitary tumors:

      • Some pituitary tumors:

        1.  Release growth hormone in response to TRH (acromegaly).

        2.  Release ACTH in response to TRH (Cushing's disease).

        3.  Failure to release prolactin (prolactinoma).

Thyroid-Stimulating Hormone (Thyrotropin, TSH)

• Overview:  thyrotropin, TSH

  • Anterior pituitary hormone.

  • Thyroid function regulation involves stimulation of thyroxine and triiodothyronine production and release.

• Chemistry:  thyrotropin, TSH

  • Consists of two peptides (A and B) with associated carbohydrate side chains

  • Therapeutic thyrotropin:

    • Source:  Recombinant human TSH

    • TSH-b subunit provides thyroid specificity since TSH-a subunit is nearly identical to a subunit of FSH, LH, hCG.

• Pharmacokinetics:  thyrotropin, TSH

  • Route of Administration:

    • Intramuscular

    • Subcutaneous

  • Half-life: one-hour

  • Renal degradation

• Pharmacodynamics:  thyrotropin, TSH

  • Thyrotropin :   thyroid cell adenylyl cyclase activation→ increased cyclic AMP production: → increased iodine uptake:  →increased thyroid hormone production

• Clinical Use:  thyrotropin, TSH

  • Diagnostic/therapeutic:

    • Possible diagnostic use in a metastatic thyroid carcinoma.

    • Possibly effective therapeutic stimulation of radioactive iodine uptake for treatment of metastatic thyroid carcinoma.

 

 

Fitzgerald, P.A. and Klonoff, D.C. Hypothalamic and Pituitary Hormones, in Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, pp 603-618.

Primary Reference: Biller, Beverly M. K. and Daniels, Gilbert, H. Neuroendocrine Regulation and Diseases of the Anterior Pituitary and Hypothalamus, In Harrison's Principles of Internal Medicine 14th edition, (Isselbacher, K.J., Braunwald, E., Wilson, J.D., Martin, J.B., Fauci, A.S. and Kasper, D.L., eds) McGraw-Hill, Inc (Health Professions Division), 1998, pp 1972-1998