51: Pituitary Hormones II Flashcards
Hypothalmic-pituitary-endocrine gland axis
Slide 5
Growth hormone functions
-aka somatotropin
-req during childhood and adolescence for normal size
-inc production of insulin-like growth factor I in liver bone cartilage muscle
-anabolic in muscle = inc lean body mass
-catabolic in lipid cells = reduce central adiposity
-reduction in insulin sensitivity
Growth hormone reduction in insulin sensitivity
-compensated by insulin activity of IGF-1
Deficiency of GH
-failure to reach adult height
-disproportional body fat
-dec muscle mass
Growth Hormone structure
-191-amino acid protein w 2 disulfide bonds
-similar to that of prolactin
-recombinant form
Growth Hormone metabolism
-20-25 min half-life
-cleared by liver
-rhGH admin SC and active for 36 hrs
Growth Hormone clinical use
-GH deficiency
-treat short kids (Willi or Turner syndrome)
-performance enhancer in athletics
-anti-aging?
-antiobesity
-use of rbGH in dairy
GH deficiency causes
-genetic
-damage to pituitary or hypothalmus
GH deficiency leads to
-short and fat
-HYPOglycemia due to unopposed insulin
Mecasermin
-rhIGF-1
-treat SEVERE IGF-1 deficiency
-complexed with rhIGFBP-3 to maintain half-life
-HYPOglycemia may occur
IGF-1 deficiency
-not responsive to exogenous GH
-mutations in GH receptor or GH neutralizing antibodies
Mecasermin side effect
-maybe HYPOglycemia
-due to insulin activity of rhIGF-1
GH ANTAgonists use
-treat GH secreting pituitary adenomas
-acromegaly
-gigantism
GH ANTAgonist drugs
-Octreotide
-Lanreotide
-Pegvisomant
Somatostatin analogs
-Octreotide
-Lanreotide
Pegvisomant
-GH ANTAgonist
-PEG derivative
-binds GH but blocks signal
Prolactin structure
-198-aa
-anterior pituitary
-similar to GH
Prolactin function
-lactation
Prolactin inhibited by
dopamine
Prolactin deficiency
-rare pituitary abnormality
-no prep of prolactin is available
Hyperprolactinemia
-caused by prolactin-secreting adenomas
-inhibit GnRH release
-amenorrhea and galactorrhea
-loss of libido/fertility in men
Hyperprolactinemia treatment
-dopamine agonists
Vasopressin and oxytocin
-posterior pituitary hormones
-synthesized in neuronal cell bodies in hypothalmus
-transported to posterior pituitary
Vasopressin and oxytocin structures
-9aa with disulfide bond
-aa diff at positions 3 and 8
-same cross activity
Desmopressin
-long acting vasopressin analog
-mod at position I and D-amino acid at 8
Vasopressin
-Antidiuretic hormone (ADH)
-arginine vasopressin (AVP)
Vasopressin released by
-posterior pituitary in response to
-rising plasma tonicity
-falling blood volume
Vasopressin function
-inc reabsorption of water (antidiuretic) (dec urine volume) (inc blood volume)
-constricts blood vessels (vasopressor)(raise BP)
-inc levels of Von Willebrand factor and coagulation factor VIII
Vasopressin metabolism
-IM or IV
-15 min half-life
-metabolized in kidney or liver
-reduction of the disulfide bond and peptide
Desmopressin metabolism
-admin IV, SC, intranasally, orally
-half-life 1.5-2.5hrs
Vasopressin receptors
-V1 and V2
V1 receptor
-GPCR that inc Ca2+
-found on vascular smooth
-mediates vasoconstriction
V2 receptor
-GPCR that increases cAMP
-renal tubule cells
-inc number or aquaporins on cell membrane = inc water permeability = water resorption
Desmopressin V receptor activity
-minimal V1 activity
-4000 times higher antidiuretic-to-vasopressor activity than vasopressin
Clinical Uses of vasopressin
-pituitary diabetes insipidus
-nocturnal enuresis
-coagulopathy in hemophilia A and von Wilderbrand’s disease
Pituitary diabetes insipidus
-deficiency of vasopressin
-polyuria
-polydipsia
-hypernatremia
-desmopressin as nasal spray, oral tablet, or by injection
Nocturnal enuresis
-bedwetting
-intranasal or oral admin of desmopressin at night
Adverse effects of vasopressin
-water intoxication
-vasopressin should be used with extreme caution in persons with CVD
-ab cramping
-allergic reaction (rare)
Vasopressin ANTAgonists
-Conivaptan
-Tolvaptan
Vasopressin ANTAgonist use
-treat hyponatremia (associated w heart failure)
-given in acute care settings
Conivaptan
-non-peptide antagonist of V1 and V2 receptors
-IV
Tolvaptan
-selective V2 receptor antagonist
-oral
Oxytocin functions
-uterine contraction in labor and delivery
-milk ejection in lactating women
-bonding, trust, love
Mech of oxytocin on uterine contraction
-contracts uterin smooth muscle
-stimulates release of prostaglandins and leukotrienes that augment uterine contraction
Mech of oxytocin on milk ejection
-contracts myoepithelial cells surrounding mammary alveoli
Oxytocin general mech
-GPCR
-inc Ca2+ –> smooth muscle constriction
Oxytocin at high concentrations
-weak antidiuretic and vasopressor activity
Clinical uses of oxytocin
-induction and stimulation of labor
-control of uterine hemorrhage after delivery (IV)
-enhancement of milk ejection (nasal spray 2-3 min prior to nursing)
Oxytocin adverse effects
-excessive stimulation of contraction before delivery
-activation of vasopressin receptors by overdose of oxytocin
Excessive stimulation of contraction before delivery
-fetal distress
-placental abruption
-uterine rupture
-trauma to birth canal
activation of vasopresssin receptors by overdose of oxytocin
-excessive fluid retention
-water intoxication
-hyponatremia
Oxytocin contraindications
-fetal distress
-abnoraml fetal presentation
-cephalopelvic disproportion
