lecture 8 (hypothalamic hormones)

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)