The hypothalamus-pituitary axis - Part 2 Flashcards
What are the landmarks of where the pituitary is located?
The pituitary is enclosed by the bony Sella Turcica, with the Diaphragm Sella located Superior and Sphenoid sinus located inferiorly.
The Optic Chiasma is a good landmark for identification of the pituitary as is white on a scan so can know pituitary is below
Sphenoid sinus is route for pituitary access -transphehnidaladenectomy
What 2 features is the pituitary broken down into, and what can these be further subdivided into?
Adenohypophysis (anterior pituitary) has three parts (labelled green;
- Pars distalis (Lobe structure - Lots of cell nuclei hence bigger)
- Para tuberalis (Suspends pituitary from hypothalamus)
- Pars intermedia (Just a line of cells, adjacent to posterior pituitary - Poorly developed in humans)
Neurohypophysis (posterior pituitary) has two parts (labelled yellow);
- Pars nervosa
- Pituitary stalk (Extension of stalk, axon neural tissue from SON and PDN)
Adenohypophysis and neurohypophysis differ in embryological development and anatomy
Pars nervosa doesn’t take up stain well as has cell nuceli, pars distallis has lots of trophic cells with cell nuclei so takes up stain well
If a patients had a change in skin tone and their blood was positive for Alpha MSH what would be the pathology?
Pars Intermedia Adenoma - Poorly developed in humans, used in animals to produce alpha MSH
Can get Pituitary Adenomas which will be positive for alpha MSH so can locate to here and patient will see a change in skin colour
Where does the Anterior Pituitary develop from embryologically?
Anterior Pituitary: Upward growth of oral ectodermal cells from Rathke’s Pouch (oral ectoderm origin)
Where does the Posterior Pituitary develop from embryologically?
Posterior Pituitary: Downward growth of neural tissue from infundibulum (neuroectoderm origin)
What can happen to the residual tissue of the pharyngeal hypophysis ?
The residual tissue of the pharyngeal hypophysis can become neoplastic and form hormone secreting tumours - called Craniopharyngiomas
What are the types of cells we have in the anterior pituitary and how are they organised ?
Anterior pituitary cell types and hormones;
- Thyrotropes (5%) = Thyroid stimulating hormones (TSH)
- Somatotropes (50%) = Growth Hormone (GH)
- Corticotropes (15%) = Adrenocorticotropic hormone (ACTH), from pro-opiomelanocortin (POMC)
- Lactotropes (15%) = Prolactin (PRL)
- Gonadotopes (10%) = Follicle-stimulating hormone (FSH) and Lutenising hormones (LH)
Give a summary of the Anterior Pituitary Hormones, the cells they’re produced in, their chemistry and Physiological Action?
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Where is Growth Hormone (GH) made, its chemistry and Physiological action?
Growth Hormone (GH);
- Made in Somatotropes
- Chemistry; Single chain of 191 amino acids
Physiological Action;
- Stimulates body growth
- Stimulates secretion of insulin-like growth factor 1
- Stimulates lipolysis
- Inhibits actions of insulin on carbohydrate and lipid metabolism
Where is Adrenocorticotropic hormone (ACTH) made, its chemistry and Physiological action?
Adrenocorticotropic hormone (ACTH)/(Corticotropin);
- Made in Corticotropes
- Chemistry; Single chain of 39 amino acids
Physiological Action;
- Stimulates production of glucocorticoids and androgens by the adrenal cortex
- Maintains size of Zona Fasciculata and Zona Reticularis of cortex
Where is Thyroid-stimulating hormone (TSH)/(Thyrotropin) made, its chemistry and Physiological action?
Thyroid-stimulating hormone (TSH)/(Thyrotropin);
- Made in Thyrotropes
- Chemistry; Glycoprotein of two subunits, a; 89 amino acids, B; 112 amino acids
Physiological Action;
- Stimulates production of thyroid hormones by thyroid follicular cells
- Maintains size of follicular cells
Where is Follicle-stimulating hormone (FSH) made, its chemistry and Physiological action?
Follicle-stimulating hormone (FSH);
- Made in Gonadotropes
- Chemistry; Glycoprotein of two subunits, a; 89 amino acids, B; 112 amino acids
Physiological Action;
- Stimulates development of ovarian follicles
- Regulates spermatogenesis in the testis
Where is Lutenizing hormone (LH) made, its chemistry and Physiological action?
Lutenizing hormone (LH);
- Made in Gonadotropes
- Chemistry; Glycoprotein of two subunits, a; 89 amino acids, B; 115 amino acids
Physiological Action;
- Causes ovulation and formation of Corpus Luteum in the ovary
- Stimulates production of oestrogen and progesterone by the ovary
- Stimulates testosterone production by the testis - shares receptor with hCG - used in pregnancy tests!
Where is Prolactin hormone (PRL) made, its chemistry and Physiological action?
Prolactin hormone (PRL);
- Made in Lactotropes
- Chemistry; Single chain of 199 amino acids
Physiological Action;
- Stimulates milk secretion and production
How does cell patterning and differentiation occur within the Anterior Pituitary?
Developing tissues are secreting growth factors BMP 2 (Ventrally) and FGF 8 (Dorsally) in a Ventral - Dorsal gradient which helps
These 2 growth factors actually oppose each other and depending on where the progenitor cells lie within the inductive gradient will turn on specific prescription factors and gene programs which causes the progenitor cells to terminally differentiate into the different trophic cells of the anterior pituitary
BMP 2 is secreted from the developing Rathke’s pouch
FGF 8 is secreted from the ventral diencephalon
Describe the mechanism by which Growth Hormone is released by?
1). Small bodied neurons in the arcuate nucelus secret growth hormone-releasing hormone (GHRH), a 43-amino acid peptide that reaches the somatotrophs via long portal veins
2). Cells in the periventricular region release somatostatin a 14-amino acid peptide, that is a potent inhibitor of growth hormone (GH) secretion, into the long portal veins
3). GNRH causes somatotrophs to synthesis and release GH
4). Somatostatin inhibits the release of GH by somtotrophs
Cellular bit;
GHRH binds to the receptor on the somatotropes, inducing the recruitment of a G-protein, a GS protein, a stimulatory G protein which then subsequently activates an enzyme adenylate cyclase. It increases cAMp stimulating protein kinase A which goes on to phosphorylate a number of protein, 1 being a specific calcium channel causing depolarisation of the cell, which then causes the secretory vesicles to diffuse with the membrane, which contain growth hormone, and once fused with the membrane release growth hormone into the extracellular fluid
Somatostatin receptor is on the same cell - another G-protein couple receptor (GPCR) attached to a different second messenger system which is activates by an inhibitory G-protein, which supresses adenylate cyclase, reducing cAMP and PKA activity - the oppose each other!
How does feedback inhibition of Growth hormone release work?
1). GH stimulates secretion of IGF-1 from peripheral target tissue (e.g liver)
2). IGF-1 directly inhibits GH release by suppressing the somatorophs
3). IGF-1 indirectly inhibits GH release by suppressing GHRH release from the arcuate nucelus in the hypothalamus (long loop feedback)
4). IGF-1 indirectly inhibits GH release by increasing the secretion of somatostatin from nuclei in the periventricular region (long loop feedback)
5). GH inhibits its own secretion via “short-loop” feedback on somatotrophs where excess growth hormone in the vicinity of the somatotrope will feedback negatively in a closed loop feedback, supressing further release
Why are Growth Hormone under Circadian Rhythms?
Because this is both under stimulatory and inhibitory regulation, growth hormone shows this pulsatile level of secretion so the circadian influence is because its under control so these different regions of the brain get input from SCN, and so growth hormone is during sleep tends to be higher, higher pulses during sleep and when you wake up these tend to be lessen and become lower pulses (still pulsatility throughout the day)
Many other pituitary hormones also show these differences in daily rhythms / diurnal secretion effects
What are the Physiological actions and consequences of Growth Hormone?
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
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
IGF and Growth hormone feedback and Inhibits GHRH release, stimulates GHIH release, inhibits GH synthesis and release.
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Give a summary of the Pituitary Hormones, the cells they’re produced in and Physiological Action?
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