06-11-23 - The hypothalamus-pituritary axis part 2 Flashcards
Learning outcomes
- Describe the anatomy and organisation of the pituitary
- Summarise the embryological development of the pituitary
- Describe the cellular organisation of the anterior pituitary
- Explain the molecular regulation of anterior pituitary development
- Review the functions of the anterior pituitary hormones
- Using GH as an example, describe how the hypothalamic-pituitary axis controls various GH actions on peripheral tissues
- Summarise the pathologies associated with GH secretion
Where is the pituitary located?
- The pituitary is enclosed by the bony sella turcica, with the diaphragma sella superior and sphenoid sinus inferior
What is the pituitary composed of?
Describe the parts of the anterior and posterior pituitary.
Which parts absorb/don’t absorb staining?
How do these 2 parts differ from each other?
- Pituitary is a compound tissue composed of 2 functionally distinct structures:
1) Adenohypophysis (anterior pituitary) has three parts (labelled green):
* Pars distalis – many cell bodies to soak up the stain
* Pars tuberalis
* Pars intermedia
2) Neurohypophysis (posterior pituitary) has two parts (labelled orange):
* Pars nervosa – white when stained, as it is largely composed of nervous tissue, with few cell bodies to soak up the stain
* Pituitary stalk
- Adenohypophysis and neurohypophysis differ in embryological development and anatomy
Describe the embryological development of the anterior and posterior pituitary.
When do these structures develop?
Describe how craniopharyngiomas form
- Pituitary: Embryonic Development
- Anterior pituitary: upward growth of oral ectodermal cells from Rathke’s Pouch (oral ectoderm origin)
- Posterior pituitary: downward growth of neural tissue from infundibulum (neuroectoderm origin)
- These structures develop between week 6 and week 16
- Craniopharyngioma hormone secreting tumours that can form when Residual tissue of the pharyngeal hypophysis can become neoplastic
What are the 5 anterior pituitary cell types?
What hormone do they each produce?
- 5 anterior pituitary cell types and the hormone they produce:
1) Thyrotropes (5%)
* Thyroid stimulating hormone (TSH)
* Alpha-beta hetero dimer (2 different subunits)
2) Somatotropes (50%)
* Growth hormone (GH)
* 191 a.a. protein
3) Corticotropes (15%)
* Adrenocorticotropic hormone (ACTH)
* 39 a.a. peptide from pro-opiomelanocortin (POMC)
4) Lactotropes (15%)
* Prolactin (PRL)
* 199 a.a. protein
5) Gonadotropes (10%)
* Follicle-stimulating hormone (FSH) and Luteinising hormone (LH)
* Alpha-beta hetero dimers
Describe the following for each anterior pituitary cell type:
1) Hormone produced
2) Chemical composition
3) Physiological action
Molecular regulation of Anterior Pituitary Development.
Describe how anterior pituitary cell types are formed?
What can happen if there is disruption in these pathways?
- Molecular regulation of Anterior Pituitary Development
- During development, there are opposing growth factors, and depending on where progenitor cells are positioned in this dorsal-ventral gradient, it will activate a group of transcription factors that will commit cells to become 1 of the 5 different anterior pituitary hormone secreting cell types
- If there is disruption of any of these pathways, it can lead to hypopituitarism and the absence of some pituitary hormones
Describe the 4 steps in the Mechanisms controlling Growth Hormone Release (in picture)
Describe the 5 steps in the Feedback inhibition of Growth hormone release (in picture)
Describe the release pattern for growth hormone.
- The release of growth hormone is pulsatile and based around the circadian rhythm
- We release the most growth hormone when we are asleep
- The pulses are due to the constant activation and inhibition of growth hormone release
Physiological Actions of Growth Hormone flowchart (in picture)
Describe 3 physiological actions of GH.
- 3 physiological actions of GH:
1) Direct anti-insulin
* Increased lipolysis in adipose tissue
* Increased blood glucose (both due to decreased glucose uptake in muscle and adipose tissue; antagonised by insulin release)
2) Indirect actions (IGF-1 release from the liver)
* Increased cartilage formation and bone growth
* Increased general protein synthesis and cell growth/division
3) Physiological consequences
* Increased linear growth and lean body mass (important for normal post-natal development and rapid growth through puberty)
* Maintains protein synthesis and tissue functions in adults
What are the 2 pathologies associated with GH?
- 2 pathologies associated with GH:
1) GH deficiency
2) GH excess (acromegaly)
What does GH deficiency lead to in kids?
How can it be treated?
- GH deficiency causes dwarfism in children due to predictable effects on linear bone growth and decreased availability of lipids and glucose for energy
- Can treated effectively with recombinant GH therapy
What is GH excess often caused by?
What is the difference between gigantism and acromegaly?
What causes gigantism?
What happens after puberty?
What are 3 effects of gigantism?
What is a treatment for gigantism?
- GH excess is often due to pituitary adenoma
- Gigantism occurs when growth hormone hypersecretion occurs before the fusion of the long bone epiphysis and is characterized by tall stature.
- Acromegaly occurs when GH hypersecretion occurs after the fusion of the epiphysis leading to large extremities and characteristic facies.
- Gigantism due to excess stimulation of epiphyseal plates
- After puberty, there is no stimulation of linear growth due to fusion of epiphyses
- 3 effects of gigantism:
1) Periosteal bone growth causing enlarged hand, jaw and foot size
2) Soft tissue growth leading to enlargement of the tongue and coarsening of facial features
3) Insulin resistance and glucose intolerance (diabetes)
- Gigantism can be treated with synthetic long-acting somatostatins (e.g. Octreotide) until transphenoidal surgery
Describe the physical signs and other symptoms associated with gigantism/acromegaly (in picture)
Hypothalamic and pituitary hormones summary (in picture)
