Biochem of Hypothalamus and Pituitary Flashcards
what 2 hormones are stored in the posterior pituitary?
- ADH- aka vasporessin (VP), arginine vasopressin (AVP)
2. Oxytocin
what kind of hormones are hypothalamic hormones
peptide that are made in neurons and released via neurotransmitter-mechanism. they have coordinated pulsatile release, and are modified by proteolytic enzymes making them functional.
What domains make AVP and OT? Are their structures similar or very different?
both have very similar structures.
AVP- AVP domain, neurophysin II, glycopeptide
OT- Ot domain, neurophysin I
What are the vasporessin receptors and what are their 2nd messengers?
V1 and V2.
V1- on the smooth muscle vasculature and the anterior pituitary. Use IP3/DAG/Ca2+
V2- on the kidney and uses cAMP
what is the function of vasopressin?
kidney– water resorption
smooth muscle vasculature– vasoconstriction
anterior pituitary– release of ACTH
**wants to decrease osmolality overall
what is the function of oxytocin?
mammary gland myoepithelium– milk production
uterine myometrium–uterine contractions
What are the oxytocin receptors and their 2nd messengers?
V1 at both the uterine myometrium and the mammary gland myoepithelium. Both use IP3/DAG/Ca2+
How is vasopressin sensed and then stimulated?
increased osmolality is sensed by osmoreceptors in the brain. mechanoreceptors the change in shape of neurons (shrink after eating salty meal) and can activate secretion of vasopressin from posterior pituitary.
- can sense 2% increase in osmolality and 10-15% decrease in BP
What is the action of AVP on the kidney collecting ducts?
AVP binds to V2 receptor and causes premade auqaporin channels (AQP2) in vesicles to fuse to the luminal membrane and allow water to flow into the blood.
What activates renin-angiotensin cycle?
decreased blood volume. Leads to increased reabsorption of Na and water, increased excretion of K+.
What is one of the few positive feedback mechanisms?
Oxytocin!
What is the role of progesterone and estrogen in the release of oxytocin?
- increased progesterone inhibits release of OT
- increased estrogen increases release of OT by increasing the number of receptors in the uterine myometrium.
What is the clinical importance of oxytocin during birth?
OT increases during birth and plateau during breast feeding. After birth, mothers who directly breastfeed release for OT which also causes uterine contraction and can act as a natural tourniquet and stop uterine bleeding.
What is a cause of diabetes insipidus?
low vasporessin or inadequate utilization of vasporessin.
What are some physical causes of defective/deficient vasopressin (ADH)?
- damage to the hypothalamus
- tumor on the posterior pituitary stalk
- any type of brain tumor interfering with hypothalamic secretion or production of ADH.
What are some genetic causes of defective/deficient vasopressin (ADH)?
- neurogenic DI–problems with the neurophysin II
2. nephrogenic DI–mutation of the V2 receptor or mutation of the AQP2 channels
What hormones are produced by the hypothalamus?
- GRH
- TRH
- CRH
- Dopamine
- GnRH
What hormones are secreted by the anterior pituitary?
- LH
- FSH
- TSH
- GH
- PRL
- POMC which gives rise to ACTH and alpha MSH
Name the glycoprotein hormones of the anterior pituitary
- TSH
- hCG
- FSH
- LH
* FSH, LH and hCG and gonadotropins
* TSH, FSH and LH are pituitary basophils
Which subunit conveys specificity of the hormone action among the glycoprotein hormones of the anterior pituitary?
the beta subunit. All have the same alpha subunit. beta gives each hormone its own specific action.
What hormones are cleaved from proopiomelanocortin (POMC)?
- ACTH
2. alpha MSH
what hormone cleaves hormones from POMC?
prohormone convertase
What are corticotropes?
Stain basophilic. Include POMC which is cleaved to ACTH, beta lipotrophic hormone, alpha-melanocyte stimulation hormone and B-endorphin. They stimulate cortisol synthesis in the adrenal gland and in excess can cause stimulation of melanin production in melanocytes
What are the pituitary somatotropes?
GH (stains acidophilic)
What are the pituitary lactotropes?
Prolactin (stains acidophilic)
What are the prolactin/growth hormone family?
have similar receptors and have both growth promoting functions as well as lactating functions. Include the pituitary somatotropes, pituitary lactotrope, and placental synchtiotroblasts.
What is Pit-1?
TF that is involved in the differentiation of thyrotropes, lactotropes and somatotropes. Involved in the expression of GH, PRL, and TSH.
What are the gonadotropes?
FSH and LH (stains basophilic)
What are the thyrotropes?
Thyrotropic hormone (stains basophilic)
What stimulates GH release from the anterior pituitary?
- hypoglycemia
- increased amino acids
- decreasing fatty acid levels
- stages III and IV of sleep
- stress
- GHRH (somatocrinin)
- Estrogen/Testosterone
- T3/T4 (essential for GH functioning)
- Ghrelin
What inhibits GH release from the anterior pituitary?
- hyperglycemia
- somatostatin (SST)
- dopamine agonists
- IGF-1 (@ anterior pituitary)
What does GH do in general?
- directly increases lipolysis in adipose tissue
- increase blood glucose levels
- increases amino acid uptake and protein synthesis
- inhibits glucose uptake in the muscle, saving it for brain and heart which run only on glucose
- increased IGF-1 synthesis and secretion
Effect of GH on the liver?
- increased IGF-1 production
- increased gluconeogenesis
- increased glycogen synthesis
Effect of GH on the bones?
causes increased growth at the epiphyseal plate. Stimulates prechondrocytes in the germinal zone to differentiate into chondrocytes and secrete IGF-1 which stimulates the chondrocytes to proliferate and grow.
Effect of GH on adipose tissue?
increased lipolysis
Effect of GH on muscle?
- decreased glucose uptake (so glucose is available for the organs that need it like the brain and the heart)
- increased protein synthesis (growth!)
What is IGF-1?
Insulin-like growth factor (similar structure and receptors). If is a mediator of GH made in the liver and inhibits the anterior pituitary from releasing more GH when the glucose levels are satisfactory. IGF has its own binding proteins that helps target GH to the tissue it is acting on. No free IGF-1 in the ECM
What does somatostatin do and what stimulates it?
Inhibits release of GHRH from the hypothalamus. Stimulated by increased glucose and fatty acids and acts via inhibitory G-proteins
What is GH deficiency?
no serious health consequences
Excess GH?
Acromegaly in adults, gigantism in children. Has serious health consequences.
