Lecture 3: Central Endocrine Glands

Where are the hypothalamus and pituitary gland?

What is the hypothalamus made up of?

brain nuclei: paraventricular nuclei (PVN) and supraoptic nuclei (SO)

synthesise hormones that are important in the posterior part of the pituitary gland 

brain nuclei

collections of cells that

what does the hypothalamus do?

• a collection of brain nuclei that have important control and integrative functions

• important for homeostasis and primary functions

• controls autonomic function via the brainstem autonomic centres

• controls endocrine function via the pituitary gland 

what does the hypothalamus respond to?

environmental factors:

• light (circadian rythym)

• stress (fear, noise, etc)

neural signals:

• visceral afferents from the intestines, heart, liver, stomach (mediated by neurotransmitters)

hormones: -ve

which pituitary hormones does TRH correspond to?

TSH, PRL, FSH

RH (ex: TRH)

releasing hormone (ex: thyroid releasing hormone)

which pituitary hormones does GnRH correspond to?

LH, FSH

which pituitary hormone/s does GHRH correspond to?

GH

which pituitary hormones does somatostatin correspond to?

GH

which pituitary hormones does CRH correspond to?

ACTH

which pituitary hormones does dopamine correspond to?

PRL

Outline the regions of the pituitary gland

Anterior + posterior

Anterior = pituitary hormones regulated by secreted hypothalamic factors

• capable of making and storing its own hormones

Posterior = pituitary hormones synthesised in hypothalamus and transported via neuronal projections

• Structurally continuous with the hypothalamus of the brain, to which it remains attached by the hypophyseal/pituitary stalk

• cannot make its own hormones, stores hormones made in the hypothalamus

tropic hormones

a hormone that activates another gland- have other endocrine glands as their target

most of the hormones produced by the hypothalamus = tropic 

ADH

antidiuretic hormone

produced in PVN (left side of the pituitary gland)

list the anterior pituitary hormones

TSH, ACTH, LH/FSH, GH, PRL

list the posterior pituitary hormones

ADH/vasopressin, neurophysins, oxytocin

trophic

cell types that can produce their own hormone (ex: thyrotroph)

outline thyrotrophs

• anterior

• Hormone = TSH

• function = thyroid hormone regulation

rare to have functional tumors

outline corticotrophs

• anterior

• ACTH

• regulation of adrenal cortex

functional tumors such as cushing’s 

outline gonadotrophs

• anterior

• LH/FSH

• reproductive control

outline somatotrophs

• GH

• growth

• anterior

functional tumors = acromegaly

outline lactotrophs

• anterior

• PRL

• milk production

functional turmors = prolactinoma

outline ADH

water regulation

outline neurophysins 

important in ADH synthesis

outline oxytocin

important in birth and breast milk expression

what makes up the majority (half) of all cell types in the anterior pituitary?

somatotrophs

the proportion of the remaining cell types can change during breastfeeding, pregnancy, etc

list the glycoproteins of the anterior pituitary hormones

TSH = thyroid stimulating

FSH = follicle stimulating
LH = luteinising

all tropic

list the proteins and polypeptide hormones of the anterior pituitary 

ACTH = adrenocorticotrophic 

GH = growth 

prolactin 

all share common alpha subunit, differ in their specialised subunit

what is a glycoprotein

a protein that has been glycosylated 

what are the single chain protein hormones?

prolactin, growth hormone

what are the two-chain glycoprotein hormones?

TSH, LH, FSH

have a common alpha subunit and unique beta subunit

outline TSH

thyrotropin and thryotrophin

made in thyrotrophs in response to pulsatile TRH release from the hypothalamus 

+ve: production of thyroid hormone TRH by hypothalamus, act on anterior pituitary, to release TSH, acts on thyroid to produce T4 prohormone, converted to T3 hormone and acts on TT

-ve: T3 acts on TT, feedback to ant. pituitary and hypothalamus to tell them to stop 

T4 acts on ant. pituitary and hypothalamus as well 

what happens when the cells in the anterior pituitary are damaged

secondary hypothyroidism- pituitary failure

secondary hyperthyroidism- pituitary tumor

primary disorder vs a secondary disorder

primary: gland itself is damaged/has an issue

secondary: disorder is caused by issue elsewhere than gland

gonadotrophins

LH and FSH

made in the gonadotrophs of the anterior pituitary in response to gonadotrophin releasing hormone (GnRH)

LH and FSH

good examples of g-protein receptors! use cAMP and protein kinase a

regulate reproduction (testosterone biosynthesis, menstruation, fertility)

adenocorticotrophic hormone (ACTH) aka adrenocorticotrophin

synthesised in corticotrophs

influences the adrenal cortex

synthesised from POMC = processing of POMC produces ACTH which acts on the adrenal cortex to produce adrenal hormones

effects of ACTH

stimulates g-protein receptor coupled to cAMP 

this stumulates the enzymes that convert cholesterol to cortisol or sex steroid precursers 

prolactin

made in lactotrophs

regulation: prolactin production inhibited by dopamine (also produced by hypothalamus).

upregulated by thyroid hormones

suckling, sleep and stress stimuli impact hypothalamus, dopamine levels drop, prolactin produced

outline some effects of prolactin

1. stimulates mammary gland development

   1. DNA synthesis, epithelial cell proliferation, synthesis of lactose + free fatty acids

2. maintains lactation

   1. synergised by glucocorticoids

   2. inhibited by oestrogen and progesterone

prolactinomas

tumor in pituitary gland, causes prolactin production

causes inappropriate expression of milk 

interferes with the HPG axis- causes infertility, amenorrhoea, galactorrhoea

treated with dopamine agonists

NB hypothyroidism —> hyperprolactinaemia due to elevations in TRH

growth hormone

pulsatile secretion w/many inputs

released throughout life, stimulated by low glucose, exercise, sleep

DOES NOT act upon bones and growth itself- stimulates liver to produce IGF1 to allow for growth

list the stimulatory factors that regulate growth hormone release

GHRH

Dopamine

Catecholamines

Excitatory amino acids

Thyroid hormone

list the inhibitory factors regulating growth hormone release

somatostatin

IGF-1

glucose

FFA

what can go wrong if you have incorrect levels of GH?

deficiency/resistance: due to receptor mutations such as Laron syndrome dwarfism, treated with IGF-1

deficiency: treated w/recombinant hGH

excess: acromegaly in adults or children, large jaw and hands 

list some causes of hypopituitarism

1. pituitary tumor

2. brain surgery

3. trauma such as road accidents

4. radiotherapy

5. blocked blood supply, bleeding, inflammation

6. autoimmunity

7. infection

arginine vasopressin/antidiuretic hormone (ADH)

nonapeptide (9 peptides) secreted from the PP

synthesised and packed with a carrier protein called neurophysin in secretory granules in the magnocellular neurones of the PV and SO nuclei

granules move down to the ends of the fibres

both released upon stimulation of the nerves

how does ADH secretion and plasma osmolarity work?

• ADH acts on the collecting ducts of the kidney

• collecting ducts intrinsically impermeable to h2o

• ADH stimulates the production of water channels and their incorporation into the walls of the collecting ducts

• this allows for the reabsorption of free water from tubular fluid

• can convert very dilute urine into very concentrated urine 

ADH excess

• caused by damage to head, secreting tumors, etc

• syndrome of inappropriate ADH secretion (SIADH)

  • water retention (low serum sodium conc) leads to highly concentrated urine

hyper

ADH deficiency

hypo- excess water excretion

diabetes insipidus

ADH needed for water absorption in the renal collecting ducts

ADH controls serum osmolarity- during water deprivation, ADH levels should rise to allow water reabsorption with an associated increase in urine concentration and reduced urine volume

if the PP is damaged, ADH may be reduced or urine cannot be concentrated

secondary to generalised pituitary disease or isolated/idiopathic

causes: polyuria (peeing too often), polydipsia (drinking too often), hypernatraemia and increased serum osmolarity

oxytocin

• stimulates contraction of smooth muscle (myoepithelial cells) of breast and uterus

• POSTIVE FEEDBACK!

• roles in milk ejection reflux and birth (parturition)

• neuro-endocrine reflexes: neuro-endocrine cells secrete hormones from the neural axon terminals into the blood in response to some neural signal