Hypothalamus, anterior and posterior pituitary gland

Outline the location of the hypothalamus

1. diencephalon

2. beneath the thalamus

3. at the floor of the third ventricle

Give 7 input examples into the hypothalamus

1. blood

2. cerebral cortex

3. hippocampal formation

4. amygdala

5. septal area

6. retina

7. ascending neural afferents

What are the 3 main things from the blood that are measured?

1. temp

2. osmotic pressure

3. hormones

What 7 hormones are monitored by the hypothalamus

1. leptin

2. triiodothyronine

3. cortisol

4. oestrogens

5. progesterone

6. androgens

7. ILGF-1

What are the 3 methods of detection in the hypothalamus

1. direct sensing via receptors

2. indirect via blood

3. indirect via nerves

Name the 6 nuclei of the hypothalamus

1. paraventricular PVN

2. supraoptic SON

3. suprachiasmatic SCN

4. lateral LN

5. arcuate AN

6. mammillary

What are each of these nuclei functions in the hypothalamus?

1. paraventricular PVN

2. supraoptic SON

3. suprachiasmatic SCN

4. lateral LN

5. arcuate AN

6. mammillary

1. oxytocin, ADH, TRH, CRH

2. oxytocin and ADH

3. biological clock/circadian

4. arousal, hunger

5. energy, GnRH, GHRH, NP-Y

6. wakefulness

What are the two mechanisms of hypothalamic input

1. humoral

2. neural

What 3 neuronal areas are sensed in the hypothalamus (indirectly?)

1. visceral and somatic sensory nerves

2. limbic system (emotions)

3. reticular activating system - eyes

Outline thermoreception in the hypothalamus: HEAT

• neurones in the anterior hypothalamus

  • heat → thermoregulation cooling centre → peripheral vasodilation etc.

Outline thermoregulation in the hypothalamus: COLD

• neurones in the posterior hypothalamus

  • thermoregulatory heating centre → peripheral vasoconstriction etc.

Outline osmoregulation in the hypothalamus

• direct measuring: respond to an increase in blood osmolarity = haemoconcentration dehydration

response:

• ADH released from SON

• secreted via posterior pituitary

• kidneys retain water

• thirst centre stimulated in LN

Outline satiation in the hypothalamus (hunger)

• Arcuate nucleus

• detect blood glucose + hormones →

  • leptin → fullness

  • ghrelin → hunger

what are the centres that respond to:

1. satiety

2. appetite

What do they detect?

1. satiety - high glucose levels → inhibits eating

2. appetite centre - low glucose levels → stimulates eating

what is the scientific word for:

1. fullness

2. hunger

1. anorexigenic

2. orexigenic

What is released from the small intestine in response to the hypothalamus stimulating appetite?

1. CCK: cholecystokinin produced

2. stimulates pancreatic secretion and gall bladder contraction

How does the biological clock work?

1. light hits retina

2. retina → SCN in the hypothalamus

3. hypothalamus stimulates pineal gland to prevent serotonin conversion to melatonin (therefore wake up)

what are the three rhythms

1. circadian

2. ultradian (<24hrs)

3. infradian (>24hrs)

What is the clinical relevance of understanding biological rhythms?

• may need to take more than one blood sample to compare hormone concentration e.g. cortisol peaks in the morning, peaks and troughs throughout the day.

What hormones does the neurohypophysis secrete?

• ADH

• oxytocin

How are hormones released from the neurohypophysis?

1. produced in hypothalamus

2. travel down neurones into neurohypophysis

3. terminate on blood vessels and release hormone directly into circulation

4. posterior pituitary - storage site, not a true endocrine gland

What is the name of the circulation within the adenohypophysis

• pituitary portal circulation

Outline how the hypothalamus and adenohypophysis are connected

1. hypothalamic neurones terminate on plexus capillaries

2. primary plexus in the hypothalamus

3. hypophyseal portal veins connect to the adenohypophysis

4. secondary plexus within it.

What are the 5 releasing hormones produced by the hypothalamus?

1. CRH: corticotrophin-releasing hormone

2. TRH: thyrotropin releasing hormone

3. GHRH: growth hormone releasing hormone/somatotropin releasing hormone

4. GnRH: gonadotrophin releasing hormone

5. PRL-RH: prolactin releasing hormone

What are the 3 inhibitory hormones produced by the hypothalamus?

1. GHIH/somatostatin: growth hormone inhibitory hormone

2. GnIH: gonadotrophin inhibitory hormone

3. Dopamine: inhibits prolactin and other hormones

what do each of these hormones trigger to be released in the pituitary gland and what are the target organs thereafter:

1. GnRH+GnIH

2. CRH

3. TRH

4. GHRH + GHIH

5. PLR-RH

1. FSH + LH: testes and ovaries

2. ACTH → adrenal cortex

3. TSH → thyroid gland

4. GH → liver and other tissues

5. prolactin → mammary gland

What are these two types of secretion:

1. tonic

2. episodic

1. constant

2. pulse/surges

What do each of these hormones trigger in their target organs?

1. LH in testes

2. LH in ovaries

3. FSH in testes

4. FSH in ovaries

5. ACTH

6. TSH

7. GH

8. Prolactin

1. ledig cell growth → testosterone

2. progesterone, ovulation

3. inhibin → sperm production

4. estradiol, corpus luteum formation

5. cortisol, corticosterone

6. thyroxine, triiodothyronine

7. IGF-1

8. milk let down

is cortisol production an example of tonic or episodic secretion?

• episodic - pulsatile and ultradian rhythm

what is an example of tonic inhibition, how does it become uninhibited?

• prolactin

• remains inhibited until stimulated → TRH → GnRH → PLR e.g. nervous system from suckling on the teat

How does dopamine inhibit prolactin?

1. it’s secreted by the hypothalamus PVN → neurones

2. released from neurone and binds to cell surface receptors on pituitary cells

3. induces DAG/Ca2+, PKA intracellular signalling

4. represses release and production of prolactin from lactotroph cells of anterior pituitary

what are neurohormones?

• small peptides secreted by neurones - 3-40 amino acids

• different secretion rates: ADH + oxytocin = lots, CRH = small

Give two examples of neuroendocrine hormones and how one works

1. Dopamine 2. TRH

• Dopamine = catecholamine

• acts through adrenergic receptors → heart and blood vessel stimulation

• dopamin e= inhibitory hypothalamic hormone

What are the 5 cell types in the pars distalis of the adenohypophysis and what do they produce?

1. thyrotropes - TSH

2. corticotropes - ACTH

3. gonadotropes - FSH and LH

4. somatotropes - GH

5. lactotropes - PRL

what does the par intermedia produce in horses

• melanotropes → MSH

In the adenohypophysis which cells are:

1. acidophils

2. basophils

1. somatotropes and lactotropes

2. corticotropes, thyrotropes, gonadotropes

What 3 hormones regulate somatotropin secretion?

1. GHRH

2. somatostatin (GHIH)

3. Ghrelin (from stomach), secreted in response to food

What does the growth hormone stimulate?

1. IGF-1 secretion from the liver

• protein synthesis (anabolic effect)

• lipolysis

• inhibits insulin (therefore glucose utilsation)

How can the lactotrope staining change?

1. storing PRL: chromophil

2. no PRL stored: chromophobe

How is PRL regulated?

1. tonic inhibition by dopamine

2. TRH stimulation

3. hypertrophy during pregnancy

How are corticotrophic hormones produced?

• POMC is produced: prohormone, proopiomelanocortin

• this is cleaved into the active hormones:

  • ACTH, MSH, beta-lipotrophic hormone, beta-endorphin, enkephalin (an endorphine), CLIP (corticotropin-like-intermediate lobe peptide

How do we get from the POMC to the active hormones?

1. prohormone convertase I - in pars distalis

2. prohormone convertase II - pars intermedia

why are labradors susceptible to obesity?

• POMC mutation, key hormones aren’t produced leading to:

  • increased adiposity and body weight

  • increased food motivation

  • increased frequency in assistance dogs

How are corticotropes regulated?

1. corticotropin-releasing hormone (CRH)

2. tonic stimulation

• more CRH → increased ACTH secretion

• less CRH → decreased ACTH secretion

negative feedback loop

What two hormones do gonadotropes produce?

1. FSH

2. LH

In males how does:

1. FSH

2. LH

affect the target organ?

1. FSH - supports spermatogenesis by sertoli cells

2. maintenance of leydig cells therefore testosterone production

In females how do these hormones affect their target organ?

1. FSH

2. LH

1. follicle development and estradiol production

2. stimulates ovulation, corpus luteum development and progesterone

How is gonadotrophic hormone production regulated?

1. GnRH from hypothalamus

2. negative feedback loop

How do thyrotropes affect their target organ and how is it regulated

1. TSH → follicular cells on thyroid gland → thyroglobulin → triiodothyronine (T3) and thyroxine (T4)

2. TRH from hypothalamus and tonic stimulation

Outline the pars intermedia:

1. structure

2. cells

3. referred to as … in horses

4. what is its control method in horses

1. small cystic cavities, follicles filled with colloid

2. basophils and chromophobes

3. melanotropes

4. prohormone POMC → MSH, NOT under negative feedback control

What is a closed loop

• target cells secrete hormones that affect their own secretion

What is an open loop

• no direct feedback

• stopped by removal of a stimulus/depletion of biochemicals e.g. stimulation by milk let down

What is a positive feedback loop? Give an example

• hormone secretion increases response to feedback - an amplification process

• oxytocin in parturition → uterine contraction → stretch during delivery → nervous impulses to hypothalamus → more oxytocin

Compare short feedback loops to long feedback loops

Short: hormone from pit.gland → feedback to hypothalamus → more/less hormone

Long: hormone from gland → hypothalamus (± pit gland)

What can an adenoma in:

1. pars distalis

2. pars intermedia

3. GH-secreting pars distalis tumour

lead to?

1. ACTH and GH secretion non-function

2. nothing to note

3. affects acidophils (VERY RARE) → excess GH → alters growth and energy metabolism.

What is gigantism? What are the consequences?

• hyperactivity/neoplasia before adolescence

• all tissues grow rapidly

consequences

• hyperglycaemia (GH antagonises insulin)

• pancreatic failure (overwork)

• diabetes mellitus

• eventually pan-hypopituitarism

• microsurgery possible in some cases

What is acromegaly, what are the consequences?

1. pituitary disorders after adolescence

consequences:

1. epiphyses of bones have fused

2. bones of distal forelimb and hindlimb grow

3. membranous bones of face grow

4. mandibles grow → prognathism

5. eventual organ enlargement

6. kyphosis of vertebrae → hunchback

Identify 4 systems that do not depend on the hypothalamus/pituitary gland

1. glucose regulation - insulin, glucagon, epinephrine

2. calcium regulation - PTH, calcitonin, active vit D

3. sodium and potassium regulation

4. gastrointestinal enzyme secretion

What are the two hormones produced by the neurohypophysis?

1. ADH (also alled vasopressin)

2. oxytocin

Oultine ADH:
1. what does it act on

2. what is the result

1. distal tube of the nephron and collecting duct

2. increases permeability to water → more reabsorbed → urine is more concentrated and of smaller volume

What can result with inadequate concentration of ADH? What clinical signs may we see

1. dilute urine when it should be concentrated

• polyuria (excessive urination)

• polydispsia (excessive drinking)

What are the two receptors involved in detection of dehydration?

1. osmoreceptors

2. stretch/volume receptors

How do osmoreceptors respond to dehydration?

• found within the hypothalamus

• respond to increased osmolarity of ECF

• higher osmolarity → more ADH released → more water conserved

Define osmolarity

• no. dissolved particles per unit volume

Outline how stretch/volume receptors detect dehydration

• found in atria and veins

• respond to LARGE changes (10% decrease in blood)

• decrease in distension detected

• nervous impulse → hypothalamus

• more ADH → more water conserved

What are the most sensitive receptors to dehydration?

osmoreceptors

What is a major method for correcting dehydration?

thirst stimulation

when will large amounts of ADH be released?

an emergency!

How does ADH act on the nephron?

• targets the distal tube and collecting duct

• act on aquaporins - water channels

Where are aquaporins present in the:

1. proximal tubule

2. distal tubule

1. all membranes

2. always on basolateral membranes + only in apical membranes when ADH present

How does ADH act on aquaporins

1. binds to cell surface receptor

2. adenyl cyclase activated

3. cAMP generated

4. vesicles containing aquaporins → cell surface

5. exocytosed

6. proportional to plasma ADH concentration

7. removed via endocytosis

What is diabetes insipidus

diabetes = increased urine output

• caused by ADH dysregulation

What are the two types of diabetes insipidus, what are each caused by?

1. neurogenic → inadequate ADH release from pituitary

2. nephrogenic → inadequate response within the kidney

How can we diagnose DI?

Give ADH:

1. concentrated urine produced → neurogenic (compensates for failure to produce ADH)

2. dilute urine → nephrogenic (kidneys fail to respond to ADH)

Outline oxytocin:

1. what cells does it act on

2. two examples of its presence

3. what kind of reflex is it?

1. smooth muscle cells

2. uterine muscles during birth and induces contraction of alveoli of mammary glands

3. neuroendocrine

How does the neuroendocrine reflex of oxytocin work during parturition?

1. nerve endings in cervix are stimulated

2. afferent impulse → hypothalamus

3. neuroendocrine cells in paraventricular and supraoptic nuclei depolarise

4. oxytocin from pars nervosa secreted

5. enters cirulation

6. act on oxytocin receptors of myometrium

7. stronger uterine contractions

What are two uses of oxytocin during parturition?

1. administered to induce parturition in many species - uterine intertia

2. retained placenta - induces contractions helping to expell it.

How does oxytocin at in the mammary glands?

stimulates milk let down:

• binds to receptor on myoepithelial cells (surround alveoli and walls of small secretory ducts)

• on the long axis of the secretory duct

• duct becomes shorter and wider

• opposite effect on circular sphincter muscle → relaxation

• BOTH increase milk outflow

Why is there a high frequency of nerves in the teats?

• detect suckling/preparation for milking

What is the nervouse impulse pathway from the mammary glands?

1. superficial sensory pathways and inguinal nerve

2. afferrent sensory neurones → lumbar segments of spinal cord

3. ascend the spinal cord sensory tracts

4. to thalamus → influence cell bodies of neuroendocrine cells

5. stimulate pituitary gland secretion (posterior)

How fast is the oxytocin mammary response?

• slower than nervous - neuroendocrine

• takes 2 seconds for sensory arc and oxytocin release

• takes longer for it to be transported in circulation (20-30s)

What is the clinical relevance of oxytocin in the mammary glands?

• administered IV or IM → induces milk let down

• weak foals treated/mares being milked

• mastitis

3 bullet points to explain the effect of oxytocin on mammary glands

1. increased pressure within alveoli

2. reduces resistance in excretory ducts

3. reduces resistance in teat canal

al lead to an increased milk outflow