Flashcards in Hypothalamo-Pituitary Axis, Growth Hormone & Pituitary Disorders Deck (57)
The hypothalamus and pituitary axis form a complex, function unit, which is the major link between which 2 systems?
Endocrine and nervous systems.
What is the sella tunica?
The pituitary gland sits in the socket of the bone called sella tunica.
Together, the hypothalamus and pituitary glands modulate a wide variety of processes, list some. (7)
Body growth, milk secretion, let down, reproduction, adrenal/thyroid gland function, water homeostasis and puberty.
What different parts is the pituitary gland made up of and what are their distinct embryonic origins?
There's the infundibulum (pituitary stalk), then the anterior (adrenohypophysis)and posterior (neurohypophysis) pituitary glands. The anterior pituitary arises from the evagination of oral ectoderm (primitive gut tissue) and the posterior pituitary arises from the neuroectoderm (primitive brain tissue). The hypothalamus drops down through the infundibulum to form the posterior pituitary, so they're connected.
What is the neurocrine function of the posterior pituitary?
Oxytocin and ADH/vasopressin are made by neurosecretory cells in the supraoptic and paraventricular nuclei of the hypothalamus and transported down the nerve cell axons to the posterior pituitary, where they are stored and released into circulation to act on distant targets.
What type of chemical secreting function does the anterior pituitary gland have?
To an extent, endocrine, neurocrine, paracrine and autocrine.
Explain the neurocrine function of the anterior pituitary.
Hormones synthesised in the hypothalamus are transported down axons and stored in the median eminence before their release into the hypophyseal portal system - they stimulate/inhibit target endocrine cells in the anterior pituitary.
Explain the endocrine, autocrine and paracrine function of the anterior pituitary.
It secretes hormones into the bloodstream and as well as distant targets, has effects on neighbouring cells (and its own).
Hormones produced by hypothalamic nerve cells, can act via which 2 neurocrine pathways?
Direct effect on target tissues after release from the posterior pituitary OR,
Hormones secreted exclusively into the hypophyseal portal system, which affect endocrine cells in the anterior pituitary.
Which 2 hormones are produced in the hypothalamus for posterior pituitary release and what do they do?
OT (oxytocin) for milk let down and uterus contraction in birth.
ADH (anti-diuretic hormone/vasopressin) to regulate body water volume.
What are tropic hormones?
Tropic hormones affect the release of other hormones in the target tissues (unlike tropic hormones, which affect growth).
Name the 6 trophic hormones of the hypothalamus.
Thyrotropin releasing hormone/TRH (also mini +be prolactin effect), Prolactin-release inhibiting hormone/PIH/dopamine, corticotropin releasing hormone/CRH, Gonadotrophin releasing hormone/GnRH, Growth hormone releasing hormone/GHRH and Growth hormone inhibiting hormone/GHIH/Somatostatin.
TRH, PIH, CRH, GnRH, GHRH, GHIH.
Pathways by which hypothalamus and anterior pituitary hormones are released are often regulated by negative feedback. To illustrate the point, explain what happens when there's raised Cortisol.
Cortisol inhibits the hypothalamus from releasing corticotropin releasing hormone (CRH) and the anterior pituitary from releasing Adrenocorticotropic hormone (ACTH). ACTH also makes efforts to stop the hypothalamus producing CRH.
What are the 5 hormones produced by the anterior pituitary and their roles?
TSH - thyroid releasing hormone (secretion from gland).
PRL - prolactin for milk secretion and mammary gland development.
ACTH - Adrenocorticotropic hormone for secretion of hormones from adrenal cortex.
LH - luteinising hormone for ovulation and secretion of sex hormones.
FSH - development of eggs and sperm.
Growth is influenced by many factors, name some.
Hormones (GH is the most important endocrine regulator of postnatal growth), genetics, nutrition and the environment.
Growth hormone, produced by the anterior pituitary is a _________ hormone, with a signal peptide that must be cleaved for proper __________. It is stimulated by ______ and inhibited by ____________. The growth promoting effects are mainly indirect, via _____/somatomedins - cell of skeletal muscle and the _______ made in response to GH.
Somatostatin/GHIH - both from the hypothalamus
IGFs (insulin-like growth factors)
What is the role of GH and IGFs?
GH is essential for normal growth in childhood and teenage years, as it stimulates long bone growth (width and prior to epiphyseal closure, length). IGFs stimulate bone and cartilage growth. In adults they both help maintain muscle and bone mass, promote healing and tissue repair and modulate metabolism and body composition.
Principal control of the body is assumed by the hypothalamus, with the CVS regulating via inputs into it. When might GH fluctuation be noticed?
There is a surge in GH secretion after the onset of deep sleep, a decrease with R.E.M. sleep, an increase with stress (trauma, surgery, fever) or exercise, a decrease in glucose or fatty acids may result in a GH increase (and the opposite), fasting increases GH secretion and obesity decreases it.
Growth hormone secretion is regulated by a long loop of negative feedback, explain it.
There is IGF mediated inhibition of GHRH from the hypothalamus. It also stimulates the release of somatostatin and inhibits the release of GH from the anterior pituitary. The shorter loop is GH itself stimulating somatostatin release.
What does growth hormone deficiency in childhood lead to and how is it treated?
Pituitary dwarfism - proportionate, complete/partial deficiency - both respond to GH therapy. Height is < 3rd percentile on a standard growth chart and the rate of growth is slower than expected for a certain age. In teen years, delayed/no sexual development.
What does growth hormone excess in childhood lead to and how is this different in adulthood?
Gigantism is the result in childhood, which is rare and often from a pituitary adenoma.
In adulthood, you get Acromegaly with large extremities (hands, feet and lower jaw).
How does growth hormone exert its effects on cells?
GH exerts its effects on cells by binding to receptors (tyrosine kinase receptors) and activating Janus kinases (JAKs), with activation of signalling pathways leading to transcription factor activation and IGF production.
There are ___ IGFs in mammals (IGF2 is mainly in ________ growth). Binding proteins modulate their ___________ and actions may be paracrine and autocrine as well as ___________.
IGFs act through IGF receptors to modulate what?
Hypertrophy, hyperplasia, increased rate of protein synthesis and rate of lipolysis in adipose tissue.
Which receptors do IGFs work on?
There is cross activation with insulin receptors (with signalling pathways resulting in metabolic effects), a hybrid receptor, IGF1r (leading to mitogenic effects) and IGF2r with no resultant tyrosine kinase activity (target for lysosomal degradation).
Other than GH and IGFs, which hormones can influence growth?
Insulin, thyroid hormones, androgens, oestrogens and glucocorticoids.
When assessing a patient with a pituitary disorder, what may the clinical presentation of a pituitary tumour involve?
The mass effect on local structures leading to visual loss, a headache and abnormality in pituitary function leading to hypo/hypersecretion.
For each of the following situations, what are the consequences?
Pituitary tumour with superior growth, lateral growth or a Cavernous sinus invasion.
Superior growth impinges (puts pressure on) the optic chiasm - visual loss is bitemporal hemi-anopia (loss of half vision form the lateral sides).
Lateral growth leads to pain and double vision.
Cavernous sinus invasion (left side) leads to cranial nerve palsy (L eye compressive problems).
What happens in the case of a pituitary tumour blocks the hypothalamic control of the gland?
Levels of TSH, LH, FSH, GH and ACTH decrease, as they are no longer stimulated, but prolactin, usually under negative control, increases - Hypopituitarism.