other hormones Flashcards
Magnocellular neurosn
- Neurosecretory cells
- axons terminate in posterior lobe of pituitary
- secrete large quantities of hormone into the systemic circulation
Parvicellular neruons
- neurosecretory cells
- axons termiante at the median eminence
- secrete small quantities of hormone into PORTAL HYPOPHYSIAL SYSTEM
–> hypophysiotropic factors
–> transported to anterior pituitary
- regulate hormoen release from anterior pituitary
G-protein couple receptors
- most hormones are hydrophilic
–> bind to receptors that are inegral membrane proteins
–> many of these receptors are G-protein coupled
- Regulate activity of adenylate cycles
–> Gs increase or Gi decrease production cAMP
- Activate phospholipase C (Gq)
–> gernerate IP3 and diacyclglycerol –> increase intracellular Ca+ –> activate protein kinase C (PKC)
general themes of peptide hormone processing
- many hormones covered are peptide hormoens
- synthesized as larger precursor proteins
- specfic proteolysis releases peptide fragments
–> peptide fragments are the functional hormone
–> often several distinct proteolytic fragments are generated
–> many each have distinct biological activities
POSTERIOR PITUITARY - hormone/production
- Oxytocin and argine vasopression (AVP) are syntheisized in the cell bodies of the hypothalamic magnocelular neurons
–> secreted into systemic circulation from posterior pitutiary gland
–> Derived from proteolytic process of precursor polypeptide
- Pre-pro-hromone is synthesized on membrane assocaited ribosomes
- translocated into ER, signal sequence cleaved, routed through golgi to neurosecretory vesciles (processed on route to nerve terminal)
Oxytocin
- Stimualtes smooth muscle contraction
–> targets
- > uterus druign pregnancy = smoth mucle contraction inducing labor
- > lactating breats = promotes milk ejection
–> G-protein couple receptor = signals through activation of phospholipase C
- oxytocin release stimulated by mechanical stimualtion of uterine cervix or suckling of lactating breast
- Oxytocin release inhibited by SEVERE PAIN, FEVER, LOUD NOISE
AVP (anginine vasopressin)
- AVP stimulates water reabsorption in kidney, contraction of vascular smooth muscle
–> G-protein couple receptors
- activate adenylate cyclase –> PKA phosphoyrlates aquaporin2 –> increases water permeability of collecting duct
- activate phospholipase C –> increase Ca conc, activates protein kinase C –> smooth muscle contraction –> increases blood pressure
regulation of AVP
- AVP stimualted by:
–> chagnes in plasma osmolarity = dehydration sensed by hypothalamic neurons
–> changes in blood volume or blood pressure = decrease blood pressure and blood volume
- AVP release inhibited by hydration, increased BP and also by
–> Atrial natriuretic factors
–> Alcohol!!!!
diabetes insipidus
- Neurogenic diabetes insipidus= defect in AVP secretion = mutation in region of AVP gene encoding neurophysin II
- Nephrogenic diabetes insipidus = defect ina bility of kidney to respond to AVP
Hypophysiotropic factors
- hormones released by the parvicellular neurons
- regulate the release of hormones from the anterior pituitary gland (serve as a link between the CNS and the endocrine system)
ACTH
- Stimualtes synthesis and release of glucocorticoids from ADRENAL CORTEX (less effective in stimulating mineralocorticoid release)
- ACTH receptor is G-protein coupled –> PKA ACTIVATED
- CRH stimulates production, release, and processing of POMC (CRH release upregulated by stress
REGULATION: via short loop (ACTH–> CRH) and Long loop (cortisol –> CRH)
signaling of Growth Hormone
- Direct effects require binding to growth hormone receptor (single hormone molecule binds two receptors molecules) –> activates JAK2 –> JAK2 phosphorylates STAT5 –> phosphorylated STAT5 enters nucleus –> transcriptional control of genes
effects of growth hromone
- Direct effect
–> protein synthesis
–> transport of amino acids into cells
–> gluconeogenesis
–> lipolysis
- Indirect effects mediated by SOMATOMEDINS
–> structurally related to INSULIN
–> Insulin like growth factor I and II
Insulin like growht factors
- GH binding to receptors in liver stimulated IGF-I production and release
- IGF-I receptor has protein tyrosine kinase activity
- Binding of IGF-I activates the kinase, propagating the IFG-I signal with in the cell (triggers somatic growth and cell proliferation)
- IFG-II mainly fucntions during fetal development
–> roles and mode of action less clear
regulation of growth hormones
- Release regulated in response to GHRH (stimulates) and Somatostatin (inhibits)
–> GHRH triggers activation of PKA
- phosphorylates CREB –> actives CRE –> activation of transcription of specific pituitary transcription factor
–> somatostatin triggers a decrease in PKA activity, opposing GHRH action
IGF-I regulation of GH
- IFG-I inhibits GH secretion and stimulates secretion of somatostatin
- feedback mechanisms on GH and Hypothalamus (Somatostatin production)
what are some disorders of growth hormones
- Hypersecretion disorders
–> gigantism in children = room for long bone growth
–> acromegaly in adults = overgrowth of soft tissue
- Hyposecretion disorders
–> dwarfism in children
–> increase body fat, decreased muscle and bone mass with reduced strength and endurance in adults
Prolactin (PRL)
- related to GH (sequence and receptors)
- Main phsyiologcial effects in mammary gland
–> promotion/maintenance of milk synthesis
–> role in males is unclear (hyperprolactinemia leads to decrease libido, impotence, infertility)
describe regulationof prolactin
- released INHIBITED BY DOPAMINE
–> autogegulatory mechanisms: increase prolactin in portal hypophysial blood signals release of dopamine from dopaminergic neruons in hypothalamus
- various PRL-releasing factors postulated but pshyiological relevance unclear
Glycoprotein hormones
- LH, FSH, Thyroid stimulating hormone (TSH)
- Heterodimeric glycoprotein hormones (alpha subunits identical, difference comes from beta subunits)
- Mode of action
–> receptors are all G-protein coupled
–> Gs type G-protein, ultimately leading toa ctivation of PKA
funtions of glycoprotein
- LH
–> ovary = stimulates estrogen/progesterone secretion and gametogenesis
–> testes = stimualtes tesosterone produciton
- FSH
–> ovary = stimulates estrogen/progesterone secertion and gametogenesis
–> testes = functiosn in spermatogenesis
- TSH = thyroid gland = stimualtes all aspects of thyroid hormone sythesis and release
control of secretion of glycoprotein
- LH and FSH released from gonadotrophs in response to GnRH
–> GnRH receptor is G-protein coupled leading toa ctivation of phospholipase C and ultimately stimualtes transcription of specific beta-subunits of LH and FSH
- TSH released from thyrotrophs in response to TRH
