Posterior Piuitary Hormones and Bone Mineral Homeostasis Flashcards
Posterior Pituitary anatomy
What is Oxytocin? Its synthesis? Release?
Oxytocin is a nonapeptide structurally similar to vasopressin (antidiuretic hormone, ADH)
- Synthesized in the paraventricular nuclei and to a lesser extent the supra optic nuclei of the hypothalamus
- Secreted from the nerve endings of these neurons, which end in the Neurohypophysis (posterior pituitary)
- Other sites for synthesis include the luteal cells of the ovary, uterus and fetal membranes
- Release occurs following:
- Sensory stimuli from the cervix and vagina at birth
- Suckling by newborn
- Oxytocin enhances the frequency and force of uterine contractions under the permissive effects of estrogen priming
- Progesterone antagonizes the effects of oxytocin
- Oxytocin also stimulates milk ejection through contraction of the myoepithelium, suckling is an important stimulus
- Coordination with prolactin release is important
How does the uterus contract during chilbirth?
Childbirth – Uterine Contractility
- Progesterone inhibits contractions
- Estrogen stimulates contractions
- Near full term – posterior pituitary releases more oxytocin, uterus produces more receptors
- Directly stimulates myometrial contractions
- Stimulates fetal membranes to produce prostaglandins – synergists of oxytocin
- Stretching
- Increases contractility of smooth muscle
- Role in initiating labor
Oxytocin is the drug of choice for what? What is its side effects? What cases should Oxytocin not be used? What is its antagonist?
Oxytocin is the drug of choice for labor induction
- Also used to augment dysfunctional labor or hypotonic contractions
- Control of postpartum hemorrhage
Oxytocin (generic, Pitocin®) is usually given by IV infusion
- Nasal spray is available for postpartum lactation
Oxytocin rarely causes serious adverse effects
- Excessive stimulation of uterine contractions
- Oxytocin is contraindicated in:
- Fetal diseases
- Prematurity
- Abnormal fetal positioning
Cephalopelvic disproportion
Atosiban
- Is an oxytocin antagonist currently used outside of North America
- Atosiban is an oxytocin analogue that blocks the oxytocin receptor
- It is a vasopressin inhibitor
- Used intravenously as a labour repressant to halt premature labour
- Perceived safety concerns has hampered its approval in North America
Vasopressin (antidiuretic hormone) - Stimuli for ADH? Actions of ADH? Therapeutic uses of ADH?
Vasopressin (antidiuretic hormone)
- Vasopressin is a nonapeptide that functions as the primary antidiuretic hormone in humans
- Synthesized in the same neurofibers as ocytocin
- Stimuli for ADH:
- Increasing tonicity; osmoreceptors (hypothalamus)
- Blood pressure drop; baroreceptors
- Actions of ADH:
- Acts on the kidney to promote water retention via the V2 receptors
- Vasopressor (constriction) responses in blood vessels via V1 receptors
- Therapeutic uses of ADH:
- Vasopressin (generic, Pitressin ®)
- Desmopressin (DDAVP, generic); longer acting vasopressin analogue; no vasoconstriction
- Used in treatment for pituitary diabetes insipidus
- Nocturnal enuresis
- Administered IV, IM, or intranasal (Desmopressin)
Vasopressin Mechanism of Action
Bone mineral homeostasis - what are osteoblasts and osteoclasts?
- Osteoblasts and osteoclasts continually remodel the human skeleton in response to mechanical forced and endocrine and paracrine factors
- Osteoblasts: synthesize or build bond (b in blast for build)
- Osteoclasts: destroy boney tissue
Bone mineral abnormalities can lead to what problems?
- Calcium (& phosphate) concentrations are maintained within tight limits in the body; bone – principal reservoir
Bone mineral abnormalities can lead to many problems - Neuromuscular excitability, weakness and tetany
- Skeletal structural support disturbances
- Loss of hematopoietic capacity
What are the key hormones in bone mineral homeostasis?
- PTH (parathyroid hormone)
- Increases serum Ca2+ and decreases PO4-
- Promotes bone remodeling
- Excess PTH promotes net bone reabsorption
- Promote renal Ca2+ absorption and PO4- excretion - Vitamin D (1,25-dihydroxyvitamin D)
- Increases serum Ca2+ and PO4-
- Promotes Ca2+ and PO4- absorption by intestinal tract and kidney; promotes bone resorption
- Directly suppresses PTH production - Calcitonin (parafollicular C cells)
- Lowers serum Ca2+ and PO4-
- Inhibits osteoclast activity
- Reduces Ca2+ and PO4- reabsorption by the kidney - Estrogens
- Oppose PTH actions by slowing bone turnover
- Produce increased levels of vitamin D
What is osteoporosis and its risk factors?
- Condition of low bone mass from abnormal mineral loss resulting in weakness and easier fracture
- Vertebral bodies, distal radium, proximal femur, ribs, long bones
- Primary osteoporosis; most commonly seen in postmenopausal women – loss of estrogen production
- Risk factors:
- Female gender
- Caucasian
- Smoking
- History of prior fracture
- Age
- Low weight ad body mass index
- Familial history
What is secondary osteoporosis and its risk factors?
Secondary Osteoporosis
- = due to many other causes
- May occur perimenopausally
- May occur postmenopausally
- Accounts for a lot of male osteoporosis
- Risk Factors:
- Diet
- GI disease
- Other endocrine disease, hyperparathyroidism
- Liver disease
- Alcoholism
- Vitamin D deficiency
- Certain drugs e.g. corticosteroids
What are the regulators of adult bone mass?
- The primary regulators of adult bone mass include:
- Physical activity
- Calcium intake
- Reproductive endocrine status - Regulators are also considered preventions for the development of osteoporosis
- Pharmacologic agents can be used in the prevention and therapy of osteoporosis to:
- Decrease bone loss (resorption)
- Promote bone formation
Prevention/Therapy of Osteoporosis (5 things)
- Raloxifene (SERM, or Selective Estrogen Receptor Modulator)
- Selective actions on bone and liver estrogen receptors
- Used to treat and prevent osteoporosis
- Does not prevent hot flashes
- The use of estrogens may be limited to those individuals also suffering from hot flashes - Bisphosphonates (risendronate)
- Most successful therapy for prevention and treatment
- Inhibit osteoclast function and bone resorption
- Do not inhibit mineralization - PTH analogues
- A recombinant PTH; daily SC injections required
- It stimulates bone formation rather than inhibit bone resorption; an effect occurring at low doses of drug even given intermittently
- Used for treatment of osteoporosis - Calcitonin
- Inhibits bone resorption by osteoclasts in some patients with osteoporosis - Vitamin D (calcitriol); vit D deficient individuals
- Improve intestinal calcium absorption
- Can suppress bone remodeling
- Improve mineral density
