Growth Hormone

GH Receptor Activation

*Cell Surface Receptors* These are cell surface receptors but activation still *leads to increase in protein synthesis*.

IGF-1

*Insulin-Like Growth Factor* This can only occur in certain tissues -- the liver being the main place. Activation of IGF-1 receptors ahs the same types of effects as activating the GH receptor directly. *Endogenously, we aren't sure which effects are due to GH or IGF-1 stimulation.* This can cause the shut off of GH production because the hypothalamus and pituitary gland have the ability to sense increased levels of IGF-1.

Growth Hormone ADR

- Cranial HTN - Muscle and joint aches - Cancer

Growth Hormone Benefits

- Elongation of bone - Increase in bone mineral density - Same effects as testosterone - Increases height - Muscle mass - Nepolosis --> breakdown of fat - Increase size of organs --> but no brain

Growth Hormone Indication

- GH deficiency --> normal stature, low GH - HIV/AIDS --> increases muscle mass - Lipodystrophy --> increases muscle mass - Idiopathic Short Stature --> short parents; administration only good for 2-3 years

Growth Hormone Pathway

GHRH activates the receptors on the pituitary gland which releases the GH protein release. This hormone will go to receptors all throughout the body to activate receptors. *Still controlled by negative feedback*

Growth Hormone Overview

Just like testosterone, the levels fluctuate throughout the day. However, unlike testosterone it follows a *pulsatile manner*. This means that every *4-5 hours* there is a pulse of GH released from the pituitary gland. During the day, levels fluctuate from high to low. Similar to testosterone, in men and women, the levelof GH is low during childhood, increases during adolescents and decreases gradually as we age.

Growth Hormone Sub-Pathway

There is another way to control GH levels aside from the negative feedback pathway. The pituitary gland contains Somatostatin receptors which is released by the hypothalamus. This goes to the pituitary gland and activates the SST5 receptor. Activation of this receptor shuts off/reduces the release of GH from the pituitary gland. *On the pituitary gland we can increase the release of GH or decrease the release.*

Gigantism/Acromegaly

These patients have an excess of circulating GH which can be caused by tumor growth on the pituitary gland. This is generally caught earlier on in a child. Prior to tumor removal, we try to control GH levels so we will administer a SST5 agonist which will turn off the production of GH. Since this receptor is found in the GI, ADR include: abdominal pain and gall stones.

Growth Hormone Abuse Potential

This has the potential to be abused by athletes in an effort to increase muscle growth and prevent aging. This can also be used to increase immune function. *For this reason off-label use is not permitted for this drug -- documented need is required*

Growth Hormone Contraindications

- Leukemia within 2 years

Growth Hormone Receptor Effects (Liver)

1. Gluconeogenesis 2. Increase IGF-1