Growth Hormone
what are the average concentrations of GH in adults vs children?
Adults: 3ng/mL vs Children: 5ng/mL
when is GH secretion usually the highest?
GH secretion is highest during the 1st 2 hours of sleep - question is which effects/causes which: Does GH secretion promote sleep or vice versa?; the current theory is that surges in GH may actually promote deep sleep
briefly explain how the classic (-) feedback mechanism of GH works
GH secretion is regulated by elevated somatostatin levels that correspond to decreased GHRH levels, and vice versa when GH secretion is being promoted; the exact mechanism that controls this is unclear
what are the 2 major types of IGFs & how do they correlate to GH concentrations?
IGF 1 - which in seen more frequently in adults and is highly correlated with GH & IGF2 - which in seen more so in the fetus and is not really correlated with GH; there is a higher correlation between GH and IGF 1, than GH and IGF 2 - during puberty a rise in GH concentration correlates to a parallel rise IGF 1 concentrations
what is the primary growth regulator in fetuses?
IGF 2
what are chondrocytes and how are they effected by IGFs?
chondrocytes are cartilage forming cells & IGFs effect all aspects of their metabolism - chondrocytes are mitogenic
what is an important characteristic that has been noted about somatostatin and what could be an application for this?
everywhere it is found, it seems to have an inhibitory effect of some kind; clinicians have looked at utilizing this effect for attacking metastatic cancers, the problem they run into though, was that the general inhibitory effects could not separate/differentiate cancerous cells from normal healthy cells
IGFs cannot be produced without an adequate supply of _______________ and __________________.
insulin & carbohydrates
describe GH's basic functions
it increases cell size (hypertrophy) and cell number (hyperplasia) - so mitosis and cytokinesis; GH has a lot of metabolic effects: it increases the rate of protein synthesis, promotes the mobilization of fatty acids (to use for energy), and decreases the ratio of glucose use (it is considered a glucose sparer) - so it effects 3 major macromolecules, this is significant
what gland secretes somatostatin other than the pituitary and what effects does this have?
somatostatin can be secreted by the delta cells of the Islets of Langerhans, where it then inhibits both insulin & glucagon (which seems odd, because they are antagonists of each other)
describe acromegaly
--Hypersecretion of GH AFTER epiphyseal plate closure --Symptoms: Mandibublar growth, widening of teeth, enlargement of hands, feet etc, diabetes; this occurs post-adolescence when the long bones have already fused; these individuals won't grow taller but their soft tissues will continue to grow and their bones will thicken (kyphosis) - one distinct feature is that their fingers look like sausages; their common cause of death is suffocation due to increased swelling of the tongue and other soft tissues cutting off their windpipe; 'Andre the Giant' had gigantism that developed into acromegaly, he died from congestive heart failure
what are GH's major effects on carbohydrate metabolism?
1) Decreasing the use of glucose for energy(probably has to do with fat mobilization/metabolism), 2) Increasing glucagon deposition (since glucose isn't being used for energy, it must be stored), and 3) Decreasing the uptake of glucose by cells, which increases blood glucose concentration (this usually takes about 30 minutes, and initially there is an increase in the cellular uptake of glucose)
how does GH effect/promote protein synthesis?
1) Increasing the transport of AAs through the cell membrane from the extracellular fluid into the cells, 2) Directly effecting ribosomes, the presence of GH increases their potential to makes more proteins, 3) Increasing the transcription of DNA to form RNA, which leads to more protein synthesis taking place (though this effect takes longer to see results from than the previous 2 (around 24-48hrs), it is an upstream effect), 4) Decreasing the catabolism of proteins and AAs (working as a protein sparer - this makes sense, and prevents the body from working against itself, in this situation the body utilizes fatty acids for energy), and lastly, 5) Promoting the release of fatty acids from adipose tissue, which leads to a high conversion of fatty acids to Acetyl CoA, which can then enter into the Krebs cycle for ATP production - this is how you use fats as energy (this one, like #3 takes awhile to kick in, several hours), if the fat mobilization under the effects of GH is excessive/you start breaking down too many fats too much acetoacetic acid is formed, this can lead to ketosis (acidosis), and may lead to diabetes mellitus development - this is why GH is considered a diabetogenic hormone
how can GH raise blood glucose concentrations and why is this not necessarily a good thing?
GH are capable of directly stimulating the beta cells of the pancreas to release more insulin, however if overstimulated these beta cells will burn out/cease to function, which will lead to the development of type 1 diabetes mellitus - this is why GH is said to have a "diabetogenic effect"; also, specific increases in secretions of GH can increase blood glucose and cause pituitary diabetes
what conditions can cause GH concentrations to rise significantly?
GH concentrations can get very high after depletion of body proteins or carbohydrates, though protein depletion seems to be the more significant one of the 2 - because just adding carbohydrates doesn't correct the excess production of GH, however adding adequate protein levels does (i.e. Kawashiorkor)
how does GH effect the growth of skeletal elements?
GH does not have a direct effect on growth of skeletal elements (bone & cartilage), however they do act indirectly on them by causing the liver to produce small proteins: 'somatomedins' (a.k.a. insulin like growth factors (IGFs)), which in turn stimulate and act on bones and cartilage
describe the basic characteristics of growth hormone and its target tissues
GH does not have a specific endocrine target gland; it is an ubiquitous protein hormone, that is 191 AAs in length, that has broad, general effects on almost all body tissues; most cells in the body do respond to GH
explain the interrelatedness of growth hormone's functions and the pancreas' products and carbohydrate metabolism
GH is not be able to cause growth, etc. if a pancreas is lacking (insulin is needed) and/or if carbohydrates are missing from the diet - GH needs an adequate amount of insulin & carbohydrates to cause its natural effects
explain how IGFs move through the bloodstream and how this effects their activity levels
IGFs eventhough they are protein are bound in serum to serum bound proteins, in this state they cannot have any biological effects/they are inactive, they must be free from the carrier protein to have any physiological effects on target tissues
what are the major abnormalities/pathologies associated with GH?
Panhypopituitarism, Gigantism, and Acromegaly
describe panhypopituitarism
it is a condition marked by a significantly low secretion rate of all anterior pituitary hormones; it can be congenital (way more common) or may develop at any point in a person's life time (usually as a result of 1 of 2 types of tumors or thrombosis of the pituitary blood vessels); this may cause a special type of dwarfism, where the individual does not pass through puberty and therefore never develops any adult sexual function - now if they only lack GH, the individual will mature sexually and may reproduce, there is no mental retardation associated with this condition, their features are proportional to each other they are generally just smaller than normal adults; traditionally this condition was very hard to treat, because GH is very species specific and there was no synthetic GH available, however it can now be readily treated with hGH that is synthesized with recombinant DNA in E. coli; when it is caused by a tumor or blood clot, symptoms will include hypothyroidism, decreased libido, etc., to treat this gonadotropins are administered exogenously, because the sexual stuff really just never comes back correctly even when the tumor or clot is removed & however the administration of other synthetic anterior pituitary hormones will typically ultimately restore their function long term
what does the term diabetes actually mean and what does this have to do with its symptoms?
it means 'copious urine production,' this is because individuals with diabetes often have this symptom, increased glucose in the bloodstream may spill into the urine and, cause the water to follow it there (basic osmosis)
what hormone can effect IGFs production in fetuses and does it effect it?
prolactin can increase IGF 2 production in fetuses - IGF 2 is considered a fetal growth regulator, without is the fetus won't grow properly
what happens if a person is subjected to an excessive amount of GH post-adolescence?
since the bones have already fused, this can cause disproportionate growth of the long bone thickness as well as growth of membranous bones (i.e. jaw); this is a condition associated with a number of different pathologies
describe the structure & function of insulin like growth factors (IGFs)
the main (but not the only) source of IGFs is the liver; many of their actions are paracrine or autocrine (local mediator cells) and they do a lot of the same things that GH does and are produced by a variety of tissues; they are called 'insulin like' because in high concentrations they will mimic the action of insulin, they are also very structurally similar to insulin and will actually interact with insulin receptors; they are do also however have some other functions not related to the development of bone and cartilage; IGFs are mitogenic; the liver is the primary source of circulating IGFs; in general IGF levels correlate very well to growth in children, even more so than GH
how does the hypothalamus regulate GH secretion?
the ventromedial nucleus region (VMN) of the hypothalamus regulates GH secretion by secreting growth hormone releasing hormone (GHRH) and somatostatin (GHIH), which directly control GH secretion rates in the anterior pituitary gland; the VMN region is sensitive to hypoglycemia and hunger, it is crucial for GH regulation
why are GH related abnormalities/pathologies becoming rarer?
they are becoming rarer, because GH can now be synthesized in a lab setting
how do IGFs effect some soft tissue production?
they can stimulate/increase osteoblast replication and increase collagen and bone matrix synthesis - basically they make more of the cells that are making bone (osteoblasts - lay down/deposit bone)
how do IGFs act on the hypothalamus and the pituitary gland?
they work through classic negative feedback to promote somatostatin secretion (in the hypothalamus) to inhibit GH secretion (in the pituitary gland) - this combination of these works to indirectly and directly give IGFs (-) feedback control of GH - it causes inhibition of GH from the hypothalamus via somatostatin and it directly causing the pituitary release less and less GH
describe gigantism
this is almost increased GH secretion along with panhypopituitarism of all other anterior pituitary hormones; an individual may be 8-9 feet tall and will probably develop hyperglycemia that can will then further develop into full blown diabetes mellitus; historically, these people rarely survive into early adulthood
why will most type 1 diabetic children also have stunted growth?
this is because of the interconnectedness of GH and insulin
what effects the regulation of GH secretion?
this typically changes based on nutritional status or stress
what causes pituitary diabetes development, what are some characteristics of this condition, and how does it compare to diabetes mellitus?
when specific increases in GH secretion cause a spike in blood glucose; cells may still be able to used insulin, its ability is just depressed; the rate of glucose used by the cells is only moderately depressed in comparison to diabetes mellitus where no insulin is being made at all; the problem with pituitary diabetes is that blood glucose concentrations are refractory to insulin - adequate insulin is there, it just doesn't really have an effect on the glucose; also it is worth noting that many side effects from decreased carbohydrate metabolism, etc. that are seen with diabetes mellitus are absent in pituitary diabetes
