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Neuroendocrine system responsibilities
- growth
- metabolis
- parts reproduction
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posterior pituitary hormones
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Clinical uses for hypothalamic and pituitary hormones
- Diagnostic tool for determining hyper or hypo endocrine functions
- pituitary replacement therapy
- drug therapy
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synthesis and release of anterior pituitary hormones are controlled
hypothalamic releasing or inhibiting hormones
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all hypothalamic and pituitary hormones except _________ are peptides
prolactin-inhibiting hormone (dopamine)
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Why can't hypothal and pituitary hormones be administered orally?
they are peptides and are rapidly degraded within GI tract
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receptors for growth hormone and prolactin
- single transmembrane peptides
- hormone binding activates intracellular tyrosine kinase (JAK2)
- phosphorylation of intracellular proteins
- influence gene regulation
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All hypothalamic and pituitary hormones (except GH and prolactin) have this type of activation
- 7-transmembrane domain serpentine peptides
- activate GPCR
- adenylyl cyclase activated
- synthesis of cAMP
- activation protein kinases
- physphorylation of intracellular proteins (enzymes)
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Hypothalamic Hormones
- Growth Hormone Releasing Hormone (GHRH, Somatorelin)
- Thyrotropin-Releasing Hormone (TRH)
- Corticotropin-Releasing Hormone (CRH, Corticorelin, Ovine Aethrel)
- Gonadotropin-Releasing Hormone (GnRH or LHRH, Gonadorelin, Factrel)
- Somatostatin (Somatotropin Release-Inhibiting Hormone, SRIH)
- Prolactin-Inhibiting Hormone (PIH, Dopamine)
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Growth Hormone-Releasing Hormone aka
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Somatorelin
- naturally occuring 44 aa peptide
- Stimulates GH release from anterior pituitary
- induces a RAPID increase in plasma GH levels in normal individuals
- Stimulates GPCR
- NOT used clinically
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Thyrotropin-Releasing Hormone (TRH)
- tripeptide
- Stimulates thyrotropin release (TSH) from anterior pituitary
- Increases prolactin release
- Stim GPCR
- NOT used clinically
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Corticotropin-Releasing Hormone aka
- CRH
- Corticorelin
- Acthrel
- Ovine
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Corticorelin, Ovine, Acthrel
- peptide
- stimulates ACTH and beta-endorphin secretion from anterior pituitary
- ACTH stim production of cortisol and androgens by adrenal cortex
- Stimulates GPCR
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Clinical use Corticorelin, Ovine, Acthrel, CRH
- Differential diagnosis of Cushing's disease vs syndrome
- ACTH release by nonpituitary tumors (ectopic ACTH secretion) does not increase following CRH stimulation-diagnose Cushing's syndrome; can be from lung tumor
- ACTH from pituitary (primary) Cushing's disease constantly increases following CRH stimulation
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Pharmokinetics of Corticorelin
- Acthrel, Ovine, CRH
- IV
- plasma t1/2 = 9 min
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Adverse effects Acthrel
- Corticorelin, Ovine, CRH
- Transient facial flushing
- mild dyspnea
- hypotension
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Gonadotropin-Releasing Hormone aka
- GnRH
- LHRH
- Gonadorelin
- Factrel
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Gonadorelin (Factrel)
- decapeptide
- pulsatile doses: stimulates gonadotropin (LH and FSH) synthesis and release from anterior pituitary
- continuous dosing: inhibits gonadotropin release; produces a pharmacological castration
- stimulates GPCR
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Clinical uses Gonadorelin
- Factrel
- Diagnosis by pulsatile administration of hypogonadal states (delayed puberty)
- if it is primary hypogonadism, LH and FSH will increase with this drug
- if it is secondary hypogonadism, they will not increase
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