Lecture 15 Flashcards
What is the hypothalamic pituitary axis?
Link between endocrine and nervous system.
-hypothalamus and pituitary gland form a functional unit
Where is the hypothalamus found?
Area of brain situated beneath the thalamus
Where is the pituitary gland found?
Sits beneath hypothalamus, in socket of bone called the sella turcica
What are some processes which the hypothalamus and pituitary gland modulate?
- body growth
- reproduction (LH and FSH)
- adrenal gland function
- water homeostasis
- milk secretion/ lactation (prolactin/oxytocin)
- thyroid gland function
- puberty
What are the two parts of the pituitary gland?
Anterior and posterior pituitary gland
Posterior is not a gland because it doesn’t make its own hormones-they are produced in hypothalamus
What connects the hypothalamus and posterior pituitary?
Infundibulum (pituitary stalk)
-hypothalamus drops down through infundibulum to form posterior pituitary
What are the embryological origins of the parts of the pituitary glands?
Anterior: evagination of oral ectoderm (Rathke’s pouch)
-from the primative gut tissue
Posterior: originates from the neuroectoderm
-primitive brain tissue
What is the neurocrine function of the posterior pituitary?
Nuclei in hypothalamus (collection of cell bodies with similar function)
-paraventricular nucleus
-supraoptic nucleus
Hormones synthesised in hypothalamus and transported down nerve cells to posterior pituitary gland (neurocrine signalling)
-stored and released from posterior pituitary gland into circulation to act on distant targets
What hormones are made in hypothalamus and enter the posterior pituitary gland?
Oxytocin
ADH
What is the anterior pituitary function?
- control and release of hormones from pituitary (inhibiting/releasing hormones) via hypothalamus
- hormones synthesised in hypothalamus transported down axons and stored in the MEDIAN EMINENCE
- hormones then released into blood supply: HYPOPHYSEAL PORTAL SYSTEM
- travel down blood supply into anterior pituitary
- hypothalamic hormones stimulate/inhibit target endocrine cells in anterior pituitary
- theses secrete hormones into circulation to act on distant targets
What other functions other than endocrine does the anterior pituitary carry out?
-autocrine
-paracrine
Anterior pituitary hormones effect neighbouring cells
Function of oxytocin?
- milk let down reflex
- uterus contractions during birth (Ferguson Reflex)
What is ADH also known as?
Vasopressin
Function of ADH?
Number of aquaporin channels increase: reabsorb more water- conserve water
Regulation of water volume
What are the tropic hormones of hypothalamus?
- TRH (thyrotropin releasing hormone)
- PIH (prolactin release-inhibiting hormone: dopamine)
- CRH (Corticotropin releasing hormone)
- GnRH (gonadotropin releasing hormone)
- GHRH (growth hormone releasing hormone)
- GHIH (growth hormone-inhibiting hormone) (stomatostatin)
What are the hormones released from hypothalamus to anterior pituitary called tropic hormones?
They affect release of another hormone
have direct effect on release of anterior pituitary hormones
What is PIH also known as?
Dopamine (neurotransmitter)
What is GHIH also known as?
Somatostatin
What are the hormones produced by the anterior pituitary?
- TSH (thyroid stimulating hormone > secretion of thyroid hormone from thyroid gland)
- ACTH (adrenocorticotropic hormone > secretion of hormones from adrenal cortex)
- LH (luteinising hormone > ovulation and secretion of sex hormones)
- FSH (follicle stimulating hormone > development of eggs and sperm)
- PRL (prolactin > mammary gland development and milk secretion)
- GH (growth hormone > growth and energy metabolism. STIMULATES IGF’s)
Give an example of the negative feedback in the hypothalamic pituitary axis:
ADRENAL AXIS Stress/pain/hypoglycaemia/low BP -hypothalamus stimulates release of CRH -CRH affects the anterior pituitary -anterior pituitary releases ACTH -ACTH acts on the adrenal cortex causing it to release cortisol -cortisol affects many tissue types
- ACTH can feedback to the hypothalamus
- cortisol feedbacks to anterior pituitary or hypothalamus
What factors influence growth?
- genetics
- environment
- nutrition
- hormones (especially growth hormone: particularly in children)
What is an increase in cell number?
Hyperplasia
Growth
What is an increase in cell size called?
Hypertrophy
Growth: in growth of muscle
What is atrophy?
-decrease in cell size
-decrease in cell number
(Getting smaller)
Difference between apoptosis and necrosis?
Necrosis is cell death by damage whereas apoptosis is programmed cell death
What type of hormone is growth hormone?
Peptide hormone
-has a signal peptide which needs to be cleaved before proper folding
Where is growth hormone produced?
Anterior pituitary
Stimulated by GHRH, inhibited by somatostatin-GHIH
How are growth-promoting effects exerted?
Indirectly via insulin-like growth factors
Why is GH essential for normal growth?
- GH stimulates long bone growth prior to epiphyseal closure (children)
- IGF’s stimulates bone growth and cartilage growth
- GH and IGF’s maintain muscle and bone mass in adults an promote healing/tissue repair, and modulating metabolism and body composition
What regulates secretion of GH?
Via hypothalamus
GHRH: increases GH secretion and somatostatin: decreases GH secretion
When do you get a surge of GH secretion?
- after onset of deep sleep
- stress
- exercise
- decrease in glucose/fatty acids
- fasting
What is the short/long loop negative feedback in GH secretion?
Long loop (mediated by IGF’s)
- inhibit release of GHRH from hypothalamus
- stimulate release of somatostatin from hypothalamus
- inhibit release of GH from anterior pituitary
Short loop
-GH itself stimulating release of somatostatin.
What happens in growth hormone deficiency?
Childhood: pituitary dwarfism (proportionate type of dwarfism)
- due to complete or partial deficiency
- growth rate slower than expected
- delayed/no sexual development during teenage years
How do you treat GH deficiency?
GH therapy
What does GH excess cause?
Gigantism in childhood
- very tall
- rare
- caused by pituitary adenoma
Acromegaly
- pituitary adenoma develops in adults
- large hands/feet/lower jaw
How does GH exert its effects on cells?
-GH binds to tyrosine kinase receptors causing change of shape and it autophophorylates itself
-these activate Janus kinases (intracellular:JAKs)
-activating many signalling pathways
= transcription factor activator and IGF production
What are the 2 types of IGF’s?
IGF1 (main GF in adults)
IGF2 (involved in fetal growth)
What do IGF’s modulate?
- hypertrophy
- hyperplasia
- protein synthesis increase
- increase rate of lipolysis in adipose tissue
What is the action of dopamine?
Inhibits release of prolactin
Difference between tropic and trophic hormones:
Trophic: affect growth
Tropic: affect release of another hormone
A hormone can be both of these
What does TRH from hypothalamus cause?
Secretion of TSH which acts on the thyroid gland stimualting it to produce thyroid hormone T3 and T4, which affect metabolic rate
What does CRH from hypothalamus cause?
Secretion of ACTH which acts on the arenal gland stimulating it to produce cortisol, which responds to stress via metabolic actions
What does PIH (dopamine) from hypothalamus cause?
Inhibits secretion of prolactin which acts upon the mammary glands to encourage breast growth and milk secretion
What does GHRH and GHIH from hypothalamus cause?
GHRH:
-secretion of growth hormone which acts upon the liver to stimulate it to produce IGF’s which enhance growth/act on many other tissues to enhance growth
GHIH:
-inhibits secretion of growth hormone and therefore all of the above
What does GnRH from hypothalamus cause?
Secretio of LH/FSH
LH: acts upon ovaries in woman and testes in male, stimulating release of sex hormones
FSH: acts upon ovaries in woman and testes in male, stimulating gamete production
What is an IGF and what are they also called?
Insulin-like growth factor
-somatomedins
Which organs respond to GH?
Liver and skeletal muscle
- produce and secrete IGF’s
- growth promoting effects are usually exerted indirectly via IGF’s
When do you get a decrease in production of GH?
- during REM sleep (light sleep)
- increase in glucose or fatty acids
- obesity
Why could you develop pituitary dwarfism?
During traumatic birth
-skull becomes crushed
How do IGF’s act?
Through IGF receptors (different from GH receptors)
What types of actions other than endocrine can IGF’s exhibit?
- paracrine
- autocrine
What other hormones also influence growth?
- insulin (enhances somatic growth, interacts with IGF receptors)
- thyroid hormones (promote CNS development and enhance GH secretion)
- androgens (accelerate pubertal growth spurt, increase muscle mass, promote closure of epiphyseal plates)
- estrogens (decrease somatic growth, promote closure of epiphyseal plates)
- glucocorticoids (inhibit somatic growth: normal cells)
What can act/bind to IGF receptors?
IGF 1 (can act on all 4 receptors) IGF 2 (only act on IGF1/2 receptors) Insulin (can also act on insulin/hybrid/IGF1 receptors, NOT IGF2)
Does IGF2 receptor have tyrosine kinase activity?
No
What does dopamine decrease and why?
GH/GnRH/LH/FSH
Through dopamine D2 GPCR’s (Gi)
