Hypothalmic Pituitary Axis And Growth Hormone Flashcards
The hypothalamic pituitary axis and growth hormone:
The hypothalamic pituitary axis:
The hypothalamus and pituitary gland form a complex functional unit that serves as the major link between the endocrine and nervous systems
They both modulate a wide variety of processes - body growth, milk secretion, reproduction, lactation, adrenal gland function, thyroid gland function, water homeostasis, puberty
The pituitary gland consists of 2 parts
Anterior Pit gland
Posterior Pit gland
The ant and post pit glands have distinct embryological origins and distinct functions
The ant pit arises from evagination of oral ectoderm (Rathke’s pouch)
The post pit originates from neuroectoderm (primitive brain tissue)
The posterior pit gland is physically connected to the hypothalamus, since the hypothalamus drops down through the infundibulum to form the posterior pit
Neurocrine function of the posterior pit
Oxytocin and antidiuretic hormone produced by neurosecretory cells in the supraoptic and paraventricular nuclei of the hypothalamus
Transported down nerve cell axons to the posterior pituitary. (Good example of neurocrine signalling)
Stored and released from posterior pituitary into the general circulation to act on distant targets
NOTE: the posterior pituitary gland does not synthesise these hormones. It just releases them.
Anterior pit function
Hormones synthesised in hypothalamus are transported down axons and stored in median eminence before release into hypophyseal portal system.
These hormones stimulate (or inhibit) target endocrine cells in the anterior pituitary gland (neurocrine function).
Endocrine cells of anterior pituitary secrete a variety of hormones into the bloodstream to act on distant target cells (i.e. endocrine function).
Anterior pituitary hormones also effect neighbouring cells (autocrine and paracrine function).
2 hormones are produced in hypothalamus for release from post pit
OT Oxytocin - (Milk let down and uterus contractions during birth)
ADH Antidiuretic hormone (also called vasopressin) - (Regulation of body water volume)
Tropic hormones of the hypothalamus
6 tropic hormones produced in the hypothalamus.
These have direct effects on the release of anterior pituitary hormones
TRH Thyrotropin releasing hormone
(PRH) Prolactin releasing hormone = TRH (minor +ve control on prolactin)
PIH Prolactin release-inhibiting hormone (or the NT - Dopamine)
CRH Corticotropin releasing hormone
GnRH Gonadotropin releasing hormone (affects release of LH and FSH)
GHRH Growth hormone releasing hormone (affects release of growth hormones)
GHIH Growth hormone-inhibiting hormone (Somatostatin)
(RH= releasing hormone, IH = inhibitory hormone)
Tropic hormones affect the release of other hormones in the target tissue NOTE: Do not confuse with trophic. (Trophic hormones affect growth)
Trophic 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 IGFs
Somatostatin - inhibits GHs and their effects
Negative feedback as a method of regulation of hormone
The pathways by which hypothalamic and anterior pituitary hormones are produced are often regulated by negative feedback
Example the negative feedback of cortisol:
Stress on the body (hypoglycaemia or pain) is picked up by the hypothalamus
The hypothalamus is stimulated to produce corticotropin releasing hormone (CRH)
This travels down to the anterior pituitary which stimulates ACTH to be produced
This travels in the blood to the adrenal cortex where it stimualtes these cells to produce cortisol
Cortisol then goes in the blood to its target cells
However Cortisol and Adrenocorticotrophic hormone feed back negatively to the anterior pituitary and the hypothalamus to stop production of CRH and ACTH
Endocrine control of growth
Growth is influence by many factors - Genetics, nutrition, hormones, environment
Terms used: Necrosis (cell death by damage) Apoptosis (programmed cell death) Atrophy (decrease in cell size and number) Hypertrophy (increase in cell size) Hyperplasia (increase in cell number)
Growth hormone
Produced in the anterior pituitary:
Stimulated by hypothalamic GHRH
Inhibited by hypothalamic Somatostatin (relaeased using the enzyme GH release inhibiting hormone)
Protein hormone (191 aa) has signal peptide that must be cleaved before proper folding
Growth-promoting effects mainly exerted indirectly via insulin-like growth factors (Somatomedins)
In response to GH, cells of the Liver and Skeletal muscle produce and secrete IGFs (Insulin-like Growth Factor)
GH is essential for normal growth during childhood and teenage years:
GH stimulates long bone growth
Length & width prior to epiphyseal closure
Width only occurs after epiphyseal plate closure
IGFs stimulate both bone and cartilage growth
In adults -
GH and IGFs help maintain muscle and bone mass and promote healing and tissue repair as well as modulating metabolism and body composition
Control of GH secretion
Principal control is via the hypothalamus
GHRH (increases GH secretion)
Somatostain (decreases GH secretion)
CNS regulates GH secretion via inputs into the hypothalamus effecting GHRH and somatostatin levels
Surge in GH secretion after onset of deep sleep
Rapid eye movement (REM) sleep, decreases GH secretion
Stress (trauma) increases GH secretion
Exercise decreases GH secretion
Decrease in glucose or fatty acids leads to increase in GH secretion
Increases in glucose or FFA leads to decrease in GH secretion
Fasting increases GH secretion , obesity decreases GH secretion
GH secretion is regulated by long loop and short loop negative feedback
Long loop negative feedback:
Mediated by IGFs - these…
Inhibit release of GHRH from hypothalamus
Stimulates the release of somatostatin (inhibits GHRH) from hypothalamus.
Inhibit release of GH from anterior pituitary
Short loop negative feedback: Mediated by GH itself via stimulation of somatostatin release.
GH deficiency and excess in childhood
Growth Hormone Deficiency In childhood - results in pituitary dwarfism
A proportionate type of dwarfism - the less GH you have the smaller you are
Complete or Partial deficiency
Both types respond to GH therapy
Height below 3rd percentile on standard growth charts
Growth rate slower than expected for age
Delayed or no sexual development during teen years
Growth Hormone Excess - In childhood, results in GIGANTISM
Rare (~ 3 cases per 10,000,000 people)
Often caused by pituitary adenoma
Robert Wadlow, the tallest person ever recorded - (8 feet 11 inches) suffered from gigantism
In Adulthood leads to ACROMEGALY - pituitary adenoma after childhood Literally means large extremities •Hands •Feet •Lower Jaw
How does GH exert its effects on cells
GH receptors activate Janus kinases (JAKs) - act as tyrosine kinase receptors
Growth hormone binds between 2 growth hormone receptors
These Janus kinases are essentially tyrosine kinases - so the dimers autophosphorylate each other (or phosphorylate the opposite dimer)
Once phosphorylated they can then phosphorylate second messengers which can the activate signal pathways which go and activate transcription factors and IGF production
Insulin like growth factors (IGFs)
2 IGFs in mammals ( IGF1and IGF2)
IGF2 mainly involved in fetal growth
IGF1 major growth factor in adults
Binding proteins modulate their availability.
Actions of IGFs can be paracrine and autocrine as well as endocrine
IGFs act through IGF receptors (distinct from GH receptors) to modulate:
Cell growth (Hypertrophy)
Cell number (Hyperplasia)
Increase in the rate of protein synthesis
Increase in the rate of lipolysis in adipose tissue
Can have hybrids that consist of 1 half insulin receptor and 1 half IGF1 receptors - so can get trickling of metabolic effects but mainly mitogenic (cell division - in this case cell growth) effects
