lecture 8 (hypothalamic hormones)
TRANSCRIPT
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MOLECULAR ENDOCRINOLOGY AND IMMUNOLOGY
Hypothalamic Hormones
http://www.lifesci.susx.ac.uk/teaching/biochem/pfs/mei/
1. Hormonal and neural integration. Neuroendocrinology2. Evidence for humoral control of anterior pituitary3. Isolation of hypothalamic hormones4. TRH5. GnRH (=LHRH)6. GHRH and somatostatin7. CRH8. PIF9. Clinical aspects10. Biochemical mode of action
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The pituitary and hypothalamus
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Evidence for control of anterior pituitary by humoral (blood-borne) factors
[G.W.Harris]
1. Study of hypothalamo-hypophysial portal system - blood flows from capillary plexus in hypothalamus (median eminence) to capillary plexus in anterior pit.
2. Plate inserted into pit stalk causes decreased secretion of GH, FSH, LH, TSH and ACTH; increased secretion of PRL and ?MSH
3. Transfer of pit to kidney capsule has same effect as (2)
4. Electrical stimulation of parts of brain (esp hypothalamus) can lead to increased or decreased stimulation of pit hormones.
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ANATOMY OF THE PITUITARY GLAND
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Hypothalamus (10-9g)
Anterior pituitary (10-6g)
Thyroid (10-3g)
Peripheral tissues (1g)
Schally; Guillemin; Vale
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The hypothalamic hormones that regulate the adenohypophysis
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TSH releasing hormone (TRH)
NH-CH-CO- | CH2 |OC-CH2
=
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ANATOMY OF THE PITUITARY GLAND
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LPEAAQEEGAVTPDLPGLENVQVRPERRFLWKDLQRVRGDLGAALDSWITKRQHPGKREE
EEKDIEAEERGDLGEGGAWRLHKRQHPGRRANQDKYSWADEEDSDWMPRSWLPDFFLDSW
FSDVPQVKRQHPGRRSFPWMESDVTKRQHPGRRFIDPELQRSWEEKEGEGVLMPEKRQHP
GKRALGHPCGPQGTCGQTGLLQLLGDLSRGQETLVKQSPQVEPWDKEPLEE
Rat proTRH
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QHWSYGRPGGKRDAELIDSFQEIVEVGQLAETQRFECTTHQPRS PLRDLKGALESLIEEETGQKKI
LHRH (= GnRH)
(pyro)Glu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2
proLHRH
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Somatostatin
Precursor:
Somatostatin-28
Somatostatin-14
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GH releasing hormone (GHRH)
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[GH]
h3 6 9 12
GH SECRETION IN MALE RAT
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GH secretion
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ACTH releasing hormone (CRH)
CRH
CRH precursor
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ANATOMY OF THE PITUITARY GLAND
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OH
OH
CH2
|CH2.NH3
+
DOPAMINE
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Signalling mechanisms of CRH
From: Grammatopoulos & Chrousos (2003)