Endo 2 - Linking nerves and hormones An introduction to neuroendocrinology Historical perspectives...

Endo 2 - Linking nerves and hormones

An introduction to neuroendocrinology

•Historical perspectives

•Neurosecretory cells

•Embryology of the pituitary gland

•Anatomy and blood supply of the hypothalamic-pituitary axis

•Hormones of the posterior pituitary gland

•Hormones of the anterior pituitary gland

•Control of hormone secretions

NEUROENDOCRINE INTEGRATION

NERVES HORMONES

EFFECTOR ORGANS

The hypothalamic-pituitary axis

Historical Persepctives

• 130 A.D. Galen: pituitary gland ‘phlegmatic glandule’ secreting waste products (pituita) into the nose

• 1838 Rathke (viz Rathke’s pouch): development of the pituitary gland

• 1886 Pierre Marie: acromegaly associated with enlarged pituitary gland

• 1909 Harvey William Cushing: described the symptoms associated with hypo- and hyper- pituitarism

Phlegmatic glandule

Development of pituitary gland - Rathke (1838)

Rathke’s pouch

Pierre Marie (1886) enlarged pituitary gland associated with acromegaly

Brain-pituitary connections• 1930’s Bargmann and the Scharrers: histological studies

identified neurosecretory cells in brain projecting to the posterior pituitary

• 1930 Popa & Fielding: identified hypophyseal portal veins capillaries. Dispute as to direction of blood flow

• 1950’s Geoffrey Harris: established neurohumoral control of anterior pituitary gland

• 1969 Guilleman & Schally: identified structure of TRH

• 1970’s The decade of neuropeptides• 1980’s Gene sequencing.

Brain-pituitary connections• 1930’s Bargmann and the Scharrers:

histological studies identified neurosecretory cells in brain projecting to the posterior pituitary

• 1930 Popa & Fielding: identified hypophyseal portal veins capillaries. Dispute as to direction of blood flow

• 1950’s Geoffrey Harris: established neurohumoral control of anterior pituitary gland

• 1969 Guilleman & Schally: identified structure of TRH

• 1970’s The decade of neuropeptides• 1980’s Gene sequencing.

DEFINING HORMONES

• ENDOCRINE

• NEUROENDOCRINE

• PARACRINE

• AUTOCRINE

• INTRACRINE

Active hormone

Circulating hormone

INTRACRINE

Transduction of Transduction of nervous signal nervous signal

into an endocrine into an endocrine signalsignal

Neurosecretory Neurosecretory cellcell

Classical neurosecretory neurones• Chromaffin cells of the adrenal medulla

• Magnocellular neurones (SON & PVN) projecting to the posterior pituitary gland

• Parvicellular neurones projecting to the hypophyseal portal capillaries

C

Magnocellular Parvicellular

Neurosecretory cells (A) and sympathetic innervation of endocrine glands (B)

ANTERIOR PITUITARY

Parvicellular neurones

Magnocellular neurones

Neurosecretory cells of the

hypothalamus

Embryology of the pituitary gland

Gross anatomy of the pituitary gland

Hypothalamic nuclei

Aminergic and serotonergic

pathways of the brain

Blood supply of the neurohypophysis and adenohypophysis

Superior hypophyseal artery

Portal veins

Inferior hypophyseal artery

Hypophyseal veinsHypophyseal veins

Blood supply of the median eminence and pituitary gland

Internal carotid artery

Venous drainage of the pituitary gland

Neurones in the hypothalamus synthesise and release hormones from the posterior pituitary

Other neurosecretory cells in the hypothalamus release their hormones into the portal capillaries in which they are transported directly to endocrine cells of the anterior pituitary gland

LH, FSH, ACTH, TSH, PRL, GH

Oxytocin, vasopressin

Structure of oxytocin and vasopressin (ADH

Control of posterior pituitary hormones

Oxytocin

• Cervix/uterus

uterine contractions

• Nipples

milk ejection(neuroendocrine reflex)

Vasopressin (ADH)

• Osmoreceptors/

volume receptors

permeability of

collecting ducts(V2 receptors)

• Vasoconstriction(V1 receptors)

Control of vasopressin release and its actions

Control of anterior pituitary secretions

• Adrenocorticotrophic hormone – ACTH CRH

• Thyroid stimulating hormone – TSH TRH

GHIH (somatostatin)• Luteinizing hormone and follicle stimulating hormone

- LH & FSH GnRH

• Prolactin – PRL dopamine

(dominant control)

TRH/others

• Growth hormone – GH GHRH GHIH

(somatostatin)

Feedback control of the H-P axis

HYPOTHALAMUS

PITUITARY GLAND

EFFECTOR ORGAN

Feed

back

External stimuli

Factors controlling the release of growth hormone

and prolactin and feedback control

Factors controlling the secretion of TSH and

feedback control

Factors controlling the secretion of ACTH and

feedback control

Hypopituitary patient resulting from a tumour

Note loss of secondary sexual characteristics