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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
The pituitary and hypothalamus
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.
ANATOMY OF THE PITUITARY GLAND
Hypothalamus (10-9g)
Anterior pituitary (10-6g)
Thyroid (10-3g)
Peripheral tissues (1g)
Schally; Guillemin; Vale
The hypothalamic hormones that regulate the adenohypophysis
TSH releasing hormone (TRH)
NH-CH-CO- | CH2 |OC-CH2
=
ANATOMY OF THE PITUITARY GLAND
LPEAAQEEGAVTPDLPGLENVQVRPERRFLWKDLQRVRGDLGAALDSWITKRQHPGKREE
EEKDIEAEERGDLGEGGAWRLHKRQHPGRRANQDKYSWADEEDSDWMPRSWLPDFFLDSW
FSDVPQVKRQHPGRRSFPWMESDVTKRQHPGRRFIDPELQRSWEEKEGEGVLMPEKRQHP
GKRALGHPCGPQGTCGQTGLLQLLGDLSRGQETLVKQSPQVEPWDKEPLEE
Rat proTRH
QHWSYGRPGGKRDAELIDSFQEIVEVGQLAETQRFECTTHQPRS PLRDLKGALESLIEEETGQKKI
LHRH (= GnRH)
(pyro)Glu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2
proLHRH
Somatostatin
Precursor:
Somatostatin-28
Somatostatin-14
GH releasing hormone (GHRH)
[GH]
h3 6 9 12
GH SECRETION IN MALE RAT
GH secretion
ACTH releasing hormone (CRH)
CRH
CRH precursor
ANATOMY OF THE PITUITARY GLAND
OH
OH
CH2
|CH2.NH3
+
DOPAMINE
Signalling mechanisms of CRH
From: Grammatopoulos & Chrousos (2003)
