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 INTRACRINE Circulating hormone

Transduction of nervous signal into an endocrine signal Neurosecretory cell Transduction of nervous signal into an endocrine signal

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

Neurosecretory cells (A) and sympathetic innervation of endocrine glands (B) Magnocellular Parvicellular C ANTERIOR PITUITARY

Neurosecretory cells of the hypothalamus 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

Blood supply of the median eminence and pituitary gland Internal carotid artery Superior hypophyseal artery Portal veins Hypophyseal veins Hypophyseal veins Inferior hypophyseal 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 External stimuli HYPOTHALAMUS Feed back PITUITARY GLAND EFFECTOR ORGAN

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