hypothalamic and pituitary hormones

  1. Neuroendocrine system responsibilities
    • growth
    • metabolis
    • parts reproduction
  2. posterior pituitary hormones
    • oxytocin
    • vasopressin
  3. Clinical uses for hypothalamic and pituitary hormones
    • Diagnostic tool for determining hyper or hypo endocrine functions
    • pituitary replacement therapy
    • drug therapy
  4. synthesis and release of anterior pituitary hormones are controlled
    hypothalamic releasing or inhibiting hormones
  5. all hypothalamic and pituitary hormones except _________ are peptides
    prolactin-inhibiting hormone (dopamine)
  6. Why can't hypothal and pituitary hormones be administered orally?
    they are peptides and are rapidly degraded within GI tract
  7. receptors for growth hormone and prolactin
    • single transmembrane peptides
    • hormone binding activates intracellular tyrosine kinase (JAK2)
    • phosphorylation of intracellular proteins
    • influence gene regulation
  8. All hypothalamic and pituitary hormones (except GH and prolactin) have this type of activation
    • 7-transmembrane domain serpentine peptides
    • activate GPCR
    • adenylyl cyclase activated
    • synthesis of cAMP
    • activation protein kinases
    • physphorylation of intracellular proteins (enzymes)
  9. Hypothalamic Hormones
    • Growth Hormone Releasing Hormone (GHRH, Somatorelin)
    • Thyrotropin-Releasing Hormone (TRH)
    • Corticotropin-Releasing Hormone (CRH, Corticorelin, Ovine Aethrel)
    • Gonadotropin-Releasing Hormone (GnRH or LHRH, Gonadorelin, Factrel)
    • Somatostatin (Somatotropin Release-Inhibiting Hormone, SRIH)
    • Prolactin-Inhibiting Hormone (PIH, Dopamine)
  10. Growth Hormone-Releasing Hormone aka
    • GHRH
    • Somatorelin
  11. Somatorelin
    • naturally occuring 44 aa peptide
    • Stimulates GH release from anterior pituitary
    • induces a RAPID increase in plasma GH levels in normal individuals
    • Stimulates GPCR
    • NOT used clinically
  12. Thyrotropin-Releasing Hormone (TRH)
    • tripeptide
    • Stimulates thyrotropin release (TSH) from anterior pituitary
    • Increases prolactin release
    • Stim GPCR
    • NOT used clinically
  13. Corticotropin-Releasing Hormone aka
    • CRH
    • Corticorelin
    • Acthrel
    • Ovine
  14. Corticorelin, Ovine, Acthrel
    • peptide
    • stimulates ACTH and beta-endorphin secretion from anterior pituitary
    • ACTH stim production of cortisol and androgens by adrenal cortex
    • Stimulates GPCR
  15. Clinical use Corticorelin, Ovine, Acthrel, CRH
    • Differential diagnosis of Cushing's disease vs syndrome
    • ACTH release by nonpituitary tumors (ectopic ACTH secretion) does not increase following CRH stimulation-diagnose Cushing's syndrome; can be from lung tumor
    • ACTH from pituitary (primary) Cushing's disease constantly increases following CRH stimulation
  16. Pharmokinetics of Corticorelin
    • Acthrel, Ovine, CRH
    • IV
    • plasma t1/2 = 9 min
  17. Adverse effects Acthrel
    • Corticorelin, Ovine, CRH
    • Transient facial flushing
    • mild dyspnea
    • hypotension
  18. Gonadotropin-Releasing Hormone aka
    • GnRH
    • LHRH
    • Gonadorelin
    • Factrel
  19. Gonadorelin (Factrel)
    • decapeptide
    • pulsatile doses: stimulates gonadotropin (LH and FSH) synthesis and release from anterior pituitary
    • continuous dosing: inhibits gonadotropin release; produces a pharmacological castration
    • stimulates GPCR
  20. Clinical uses Gonadorelin
    • Factrel
    • Diagnosis by pulsatile administration of hypogonadal states (delayed puberty)
    • if it is primary hypogonadism, LH and FSH will increase with this drug
    • if it is secondary hypogonadism, they will not increase
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hypothalamic and pituitary hormones