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MOLECULAR ENDOCRINOLOGY AND IMMUNOLOGY Hypothalamic Hormones

http://www.lifesci.susx.ac.uk/teaching/biochem/pfs/mei/. MOLECULAR ENDOCRINOLOGY AND IMMUNOLOGY Hypothalamic Hormones. Hormonal and neural integration. Neuroendocrinology Evidence for humoral control of anterior pituitary Isolation of hypothalamic hormones TRH GnRH (=LHRH)

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MOLECULAR ENDOCRINOLOGY AND IMMUNOLOGY Hypothalamic Hormones

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  1. http://www.lifesci.susx.ac.uk/teaching/biochem/pfs/mei/ MOLECULAR ENDOCRINOLOGY AND IMMUNOLOGY Hypothalamic Hormones Hormonal and neural integration. Neuroendocrinology Evidence for humoral control of anterior pituitary Isolation of hypothalamic hormones TRH GnRH (=LHRH) GHRH and somatostatin CRH PIF Clinical aspects Biochemical mode of action

  2. The pituitary and hypothalamus

  3. 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.

  4. ANATOMY OF THE PITUITARY GLAND

  5. Hypothalamus (10-9g) Anterior pituitary (10-6g) Thyroid (10-3g) Peripheral tissues (1g) Schally; Guillemin; Vale

  6. The hypothalamic hormones that regulate the adenohypophysis

  7. NH-CH-CO- | CH2 | OC-CH2 TSH releasing hormone (TRH) =

  8. ANATOMY OF THE PITUITARY GLAND

  9. Rat proTRH LPEAAQEEGAVTPDLPGLENVQVRPERRFLWKDLQRVRGDLGAALDSWITKRQHPGKREE EEKDIEAEERGDLGEGGAWRLHKRQHPGRRANQDKYSWADEEDSDWMPRSWLPDFFLDSW FSDVPQVKRQHPGRRSFPWMESDVTKRQHPGRRFIDPELQRSWEEKEGEGVLMPEKRQHP GKRALGHPCGPQGTCGQTGLLQLLGDLSRGQETLVKQSPQVEPWDKEPLEE

  10. LHRH (= GnRH) (pyro)Glu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2 proLHRH QHWSYGRPGGKRDAELIDSFQEIVEVGQLAETQRFECTTHQPRS PLRDLKGALESLIEEETGQKKI

  11. Somatostatin Precursor: Somatostatin-28 Somatostatin-14

  12. GH releasing hormone (GHRH)

  13. GH SECRETION IN MALE RAT [GH] 3 6 9 12 h

  14. GH secretion

  15. ACTH releasing hormone (CRH) CRH CRH precursor

  16. ANATOMY OF THE PITUITARY GLAND

  17. OH OH CH2 | CH2.NH3+ DOPAMINE

  18. Signalling mechanisms of CRH From: Grammatopoulos & Chrousos (2003)

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