8.1 The hypothalamic pituitary axis and Growth Hormone Flashcards
what is the hypothalamic pituitary axis?
A complex functional unit that serves as the major
link between the endocrine and nervous systems. Composed of the hypothalamus and pituitary gland
where does the pituitary gland sit in relation to the hypothalamus?
The pituitary gland sits beneath the hypothalamus in a socket of bone called the sella turcica
What 8 processes do the hypothalamus and pituitary gland modulate?
body growth reproduction milk secretion lactation arenal gland function thyroid gland function water homeostasis puberty
Describe the structure of the pituitary gland?
The pituitary gland consists of 2 parts:
Anterior pituitary gland (Adenohypophysis)
Posterior pituitary gland (Neurohypophysis)
How is the pituitary gland connected to the hypothalamus?
The posterior pituitary gland is physically connected to the hypothalamus by the infundibulum (pituitary stalk)
How does the anterior pituitary gland develop?
Anterior pituitary arises from evagination of oral ectoderm
(Rathke’s pouch)
(primative gut tissue)
How does the posterior pituitary gland develop?
Posterior pituitary originates from neuroectoderm.
primitive brain tissue
What is the function of the posterior pituitary gland?
Posterior pituitary gland has a neurocrine function.
Stores and releases oxytocin and antidiuretic hormone into the general circulation to act on distant targets (endocrine). Does not synthesise them.
Where are oxytocin and antidiuretic hormone produced?
Oxytocin and antidiuretic hormone produced by neurosecretory cells in the supraoptic and paraventricular nuclei of the hypothalamus. These hormones are transported down nerve cell axons
to the posterior pituitary.
What is the blood supply to the posterior pituitary gland?
inferior hypophyseal artery
What is the function of the anterior pituitary gland?
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).
describe the blood supply to the anterior pituitary gland?
The superior hypophyseal artery enters the primary capillary plexus of hypophyseal portal system within the infundibulum.
Hypophyseal portal veins descend into the anterior pituitary gland.
What 2 distinct neurocrine pathways do hormones produced by nerve cells of the hypothalamus act by?
- Direct effects on distant target tissues via oxytocin and antidiuretic hormone from the posterior pituitary
- Hormones secreted exclusively into hypophyseal portal system affect endocrine cells within the anterior pituitary
What 2 hormones are produced in the hypothalamus for release in the posterior pituitary?
- Oxytocin OT - milk let down and uterus contractions during birth
- Antidiuretic hormone ADH (vasopressin) - regulation of body water volume
What are tropic hormones?
Tropic hormones are hormones that have other endocrine glands as their target. Most tropic hormones are produced and secreted by the anterior pituitary.
What are the 6 tropic hormones produced by the 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 (somatostatin)
What hormones are produced by the anterior pituitary?
TSH - Thyroid stimulating hormone ACTH - Adrenocorticotropic hormone LH - Luteinising hormone FSH - Follicle stimulating hormone PRL - Prolactin GH - Growth hormone
What is the function of thyroid stimulating hormone?
secretion of thyroid hormone from the thyroid gland
What is the function of adrenocorticotropic hormone?
secretion of hormones (cortisol) from adrenal cortex
What is the function of luteinising hormone?
ovulation and secretion of sex hormones
what is the function of follicle stimulating hormone?
development of eggs and sperm
What is the function of prolactin?
mammary gland development and milk secretion
What is the function of growth hormone?
growth and energy metabolism. Stimulates IGFs
What is the function of thyrotropin releasing hormone?
Stimulates anterior pituitary gland to release thyroid stimulating hormone. TSH then stimulates the thyroid gland to release the thyroid hormones T3 and T4. thyroid hormones affect the metabolic rate.
What is the function of corticotropin releasing hormone?
corticotropin releasing hormone stimulates the anterior pituitary gland to produce adrenocorticotropic hormone. ACTH stimulates the adrenal gland to produce cortisol which affects the stress response and metabolic actions.
What is the function of Prolactin release-inhibiting hormone?
Prolactin release-inhibiting hormone inhibits the anterior pituitary gland secreting prolactin.
What is the function of thyrotropin releasing hormone?
Thyrotropin releasing hormone stimulates the release of prolactin from the anterior pituitary gland. Prolactin affects the mammary glands and stimulates breast growth and milk secretion
what is the function of growth hormone releasing hormone?
Growth hormone releasing hormone stimulates the anterior pituitary gland to produce growth hormone
what is the function of growth hormone inhibiting hormone?
growth hormone inhibiting hormone inhibits the anterior pituitary gland from releasing growth hormone
What is the function of gonadotropin releasing hormone?
Gonadotropin releasing hormone stimulates the anterior pituitary gland to secrete luteinising hormone and follicles stimulating hormone.
How are hypothalamic and anterior pituitary hormones regulated?
by negative feedback
What is meant by short loop negative feedback?
The negative feedback on the hypothalamus provided by the hormone (hormone 2 in the chain) released form the anterior pituitary gland.
What is meant by long loop negative feedback?
negative feedback from end tissue/target endocrine gland to the hypothalamus
describe the hypothalamic-pituitary-adrenal axis
stress stimulates the hypothalamus to release corticotropin releasing hormone.
CRH has positive feedback on the anterior pituitary gland to release adrenocorticotropic hormone.
ACTH has positive feedback on the adrenal cortex to produce cortisol.
Cortisol has a negative feedback on both the anterior pituitary gland and the hypothalamus.
what factors influence growth?
genetics
nutrition
environment
hormones (endocrine control by growth hormone)
what is apoptosis?
programmed cell death
what is necrosis?
cell death by damage
what is hypertrophy?
increase in cell size
what is hyperplasia?
increase in cell number
what is atrophy?
decrease in cell size or number
where is growth hormone produced?
in the anterior pituitary gland
what hormones affect the production of growth hormone?
stimulated by hypothalamic GHRH
Inhibited by hypothalamic somatostatin ( growth hormone inhibiting hormone
Describe the structure of growth hormone?
Composed of a protein hormone (191 aa) that has a signal peptide that must be leaved before proper folding
How does growth hormone exert growth-promoting effects?
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 factors)
Why is Growth Hormone essential for normal bone growth during childhood and teenage years?
GH stimulates long bone growth (Length & width prior to epiphyseal closure, only width after epiphyseal closure)
GH stimulates the production of IGFs which stimulate both bone and cartilage growth
How does the function of GH and IGF vary in adults and children?
Children: GH stimulates growth of length and width of bone. IGF stimulates bone and cartilage growth
Adults: GH and IGFs help maintain muscle and bone mass and promote healing and tissue repair as well as modulating metabolism and bodycomposition.
How is growth hormone secretion controlled?
CNS regulates GH secretion via inputs into the hypothalamus effecting GHRH(stimulates) and somatostatin(inhibits) levels
How does Growth hormone secretion from the anterior pituitary gland vary throughout the day?
- Surge in GH secretion after onset of deep sleep
- Rapid Eye Movement (REM) sleep decreases GH secretion
- Stress (e.g. trauma, surgery fever) increases GH secretion
- Exercise increases GH secretion.
- Decrease in glucose or fatty acids leads to increase in GH secretion
- Increase in glucose or free fatty acid leads to decrease in GH secretion
- Fasting increases GH secretion
- Obesity decreases GH secretion.
Describe long loop negative feedback of growth hormone secretion
Long loop negative feedback is mediated by IGFs.
•Inhibit release of GHRH from
hypothalamus
•Stimulates the release of
somatostatin from hypothalamus.
•Inhibit release of GH from anterior pituitary
Describe short loop negative feedback of growth hormone secretion
Mediated by GH itself via stimulation of somatostatin release (GHIH) from the hypothalamus
What condition is a result of growth hormone deficiency in childhood?
Pituitary dwarfism
What is pituitary dwarfism?
Caused by complete or partial deficiency of growth hormone during childhood. Proportionate type of dwarfism
Height below 3rd percentile on standard growth charts
Growth rate slower than expected for age
Delayed or no sexual development during teen years
What is gigantism?
Growth hormone excess in children. Often caused by pituitary adenoma.
what is acromegaly?
Growth hormone excess in adults. Not as rare as gigantism, occurs with pituitary adenoma
occurring after epiphysial plates have ossified so not super tall. Results in large extremities (hands, feet, lower jaw)
How does GH exert its effects on cells?
GH receptors activate Janus kinases (JAKs).
Binding of GH promotes dimerisation of the tyrosine kinase receptor. Janus kinases undergo autophosphorylation. This activates the signalling pathways and IGF is produced.
Describe the structure of the growth hormone receptor
Growth hormone receptor is a type of tyrosine kinase receptors. Similar to insulin receptor.
Unlike the insulin receptor, binding of the hormone promotes the dimerisation of the tyrosine kinase receptor.
What are the main function of IGF1 and IGF2?
IGF1 major growth factor in adults
IGF2 mainly involved in fetal growth
How is the availability of IGFs modulated?
binding proteins
What is the function of IGFs?
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
what are hybrid receptors for IGFs?
hybrid IGF receptors are tyrosine kinase receptors that both insulin and IGFs both bind to. On binding, activation initiates mainly mitogenic affects (mitosis)
Apart from GH, 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