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• The endocrine system releases hormones into the bloodstream, which carries chemical messengers to target cells throughout the body
• Hormones have a much broader range of response time than do nerve impulses, requiring from seconds to days, or longer, to cause a response that may last for weeks or months
• An important function of the hypothalamus is to connect the nervous system with the endocrine system via the pituitary gland
• Hormones secreted by the hypothalamus and the pituitary

  • Peptides
  • Glycoproteins
• Releasing/inhibiting factors or hormones

  Produced in the hypothalamus, reach the pituitary by the hypophyseal portal system
• Interaction of releasing hormones with receptors

  1. Activation of genes that promote the synthesis of protein precursors

  2. Protein precursors undergo posttranslational modification to produce hormones

  3. Hormones released into the circulation
• Each hypothalamic regulatory hormone controls the release of a specific hormone from the anterior pituitary
• Pituitary hormone preparations are currently used for specific hormonal deficiencies, although most of the agents have limited therapeutic applications
• Hormones of the anterior pituitary

  Administered intramuscularly (IM), subcutaneously, or intranasally because their peptidyl nature makes them susceptible to destruction by proteolytic enzymes of the digestive tract
• Corticotropin-releasing hormone (CRH)


  Responsible for the synthesis and release of the peptide proopiomelanocortin by the pituitary
• Adrenocorticotropic hormone (ACTH) or corticotropin

  A product of the posttranslational processing of the proopiomelanocortin precursor polypeptide
• Normally, ACTH is released from the pituitary in pulses with an overriding diurnal rhythm, with the highest concentration occurring in early morning and the lowest in late evening
• Stress stimulates ACTH secretion, whereas cortisol acting via negative feedback suppresses its release
• Mechanism of action of ACTH

  1. ACTH binds to receptors on the surface of the adrenal cortex

  2. Activates G protein-coupled processes

  3. Ultimately stimulates the rate-limiting step in the adrenocorticosteroid synthetic pathway (cholesterol to pregnenolone)

  4. Pathway ends with the synthesis and release of adrenocorticosteroids and the adrenal androgens
• Therapeutic uses of ACTH

  • Differentiating between primary adrenal insufficiency (Addison disease, associated with adrenal atrophy) and secondary adrenal insufficiency (caused by inadequate secretion of ACTH by the pituitary)
  • Treatment of infantile spasms and multiple sclerosis
• Short-term use of ACTH for diagnostic purposes is usually well tolerated, but with longer use, toxicities are similar to glucocorticoids and include hypertension, peripheral edema, hypokalemia, emotional disturbances, and increased risk of infection
• Growth hormone (GH)-releasing hormone


  Stimulates the release of somatotropin by the anterior pituitary
• Somatostatin


  Inhibits the release of GH and thyroid-stimulating hormone (TSH) from the pituitary
• Synthetic analogs of somatostatin


  • Octreotide
  • Lanreotide
• Octreotide and lanreotide have found use in the treatment of acromegaly and in severe diarrhea/flushing episodes associated with carcinoid tumors
• An intravenous infusion of octreotide is also used for the treatment of bleeding esophageal varices
• Adverse effects of octreotide

  • Bradycardia
  • Diarrhea
  • Abdominal pain
  • Flatulence
  • Nausea
  • Steatorrhea
• Gonadotropins (FSH and LH)


  Produced in the anterior pituitary, regulate the production of gonadal steroid hormones
• Gonadotropin preparations


  • Menotropins (human menopausal gonadotropins or hMG)
  • Urofollitropin (FSH)
  • Follitropin alfa and follitropin beta (recombinant human FSH)
  • Human chorionic gonadotropin (hCG)
• Use of gonadotropin preparations for infertility

  1. For infertile women: Menotropin for growth and maturation of follicles, followed by hCG for ovulation

  2. For infertile men: hCG for maturation of external sexual organs, followed by menotropin for induction of spermatogenesis
• Adverse effects of gonadotropin preparations include ovarian enlargement, possible ovarian hyperstimulation syndrome, and multiple births
• Prolactin


  Peptide hormone secreted by the anterior pituitary, stimulates and maintains lactation, decreases sexual drive and reproductive function
• Thyrotropin-releasing hormone (TRH)


  Stimulates the release of prolactin
• Dopamine


  Inhibits the secretion of prolactin
• Drugs that act as dopamine antagonists (e.g., metoclopramide and some antipsychotics) can increase the secretion of prolactin
• Hyperprolactinemia


  Associated with galactorrhea and hypogonadism, treated with D2 receptor agonists like bromocriptine and cabergoline
• Bromocriptine is also indicated for the treatment of type 2 diabetes
• Vasopressin and oxytocin, the hormones of the posterior pituitary, are not regulated by releasing hormones
• Vasopressin and oxytocin are synthesized in the hypothalamus, transported to the posterior pituitary, and released in response to specific physiologic signals
• Oxytocin


  Used in obstetrics to stimulate uterine contraction and induce labor, also causes milk ejection by contracting the myoepithelial cells around the mammary alveoli
• Vasopressin (antidiuretic hormone)


  Has both antidiuretic and vasopressor effects, binds to the V2 receptor in the kidney to increase water permeability and reabsorption in the collecting tubules, used to treat diabetes insipidus
• Oxytocin


  Used in obstetrics to stimulate uterine contraction and induce labor. Also causes milk ejection by contracting the myoepithelial cells around the mammary alveoli.
• Oxytocin


  • Toxicities are uncommon with proper drug use, but hypertension, uterine rupture, water retention, and fetal death may occur. Its antidiuretic and pressor activities are much less than those of vasopressin.
• Vasopressin (antidiuretic hormone)


  Structurally related to oxytocin. Has both antidiuretic and vasopressor effects.
• Vasopressin mechanism of action

  1. Binds to the V2 receptor to increase water permeability and reabsorption in the collecting tubules

  2. Mediated by the V1 receptor, which is found in the liver, vascular smooth muscle (where it causes constriction), and other tissues