Lecture 24: Endocrine 2 Flashcards
Hormone action- steroids
- The bit of DNA to which the receptors bind is known as the “steroid response element”
- the finger like projections fit shape of the DNA helix
- the ‘fingers’ on the receptor are held in shape by zinc atoms
Hormone action- post receptor signalling.
Ie after binding what’s the next step?
After binding, 2nd step involves the stimulation of the adenyl cyclase.
This enzyme catalyses the conversion of ATP to cAMP
The cAMP is referred to as the ‘second messenger’ because it propagates the effect of the hormone.
Slide 4
Hormone action - testosterone
Dihydrotestosterone is a “pure” androgen, in that it cannot be converted to oestradiol.
Thus DHT is often responsible for the male aspects of sexual behaviour and the development of make secondary sex characteristics.
Conversion takes place at the site of action. The enzyme is located on the nuclear membrane.
Cells without 5a-reductase don’t respond to testosterone.
Mechanisms of hormone action:
What does hormone-receptor binding rely on?
Hormone receptor binding is the crucial 1st step for hormone action, however this interaction depends equally on:
- blood convention of hormone
- number of receptors
- affinity (strength) of bond
What does hormone-receptor binding rely on?
Blood concentration
Concentration on blood at any one time reflects:
- rate of hormone secretion
- amount of hormone bound to carrier proteins
- rate of degredation by liver/kidney/lungs
- concentration in blood not static
- many hormones bound bound specifically and reversibly to carrier proteins to a) reduce degredation, b) increase solubility
- hormone secretion may be episodic, pulsatile, or follow a daily rhythm
What is the duration of activity
Persistence of hormone in blood, ie half-life, varies with type of hormone; generally brief (15-30mins)
- duration of hormone action is limited, ranging from 20 minutes to several hours
- related to duration of secretion and half-life in circulation
Building proteins
- Steroids are virtually insoluble, but when bound to a binding protein their solubility in blood is increased considerably.
- in the blood stream an equilibrium develops between free steroids and the steroid-binding protein complex
- some binding proteins have endocrine actions
Prohormones
- in some cases the substance produced in the endocrine gland is not effective hormones but a “prohormone” or a prehormone
- this form of the hormone is better for transport within the endocrine cell, is resistant to uncontrolled degredation, but has very low biopotency
- it may be processed before release (eg insulin), converted in the target tissue into the active hormone (eg testosterone- DHT)
Local hormones
- the specificity of local hormones is assured by their rapid destruction.
- this, only tissues very close to the site of release will be affected.
- for example, prostaglandins are totally inactivated in blood as they pass through the lungs
What controls hormone release?
- hormone secretion is triggered by some internal/external stimulus
- synthesis and release of most hormones are regulated by negative feedback system
- as hormone levels rises they cause target organ effects that inhibit further hormone release
- therefore, many hormones vary only within a narrow homeostatic range.
In general, endocrine cells alter hormones secretion in response to 2 major types of input:
- Humoral signals
- hormones
- ions
- metabolises - Neural signals- mainly innervate the posterior pituitary gland and adrenal medulla
Pituitary gland
Anterior is its own organ
Posterior is just an extention of the brain.
The pos gland contains axonal terminals, then they release their hormones oxytocin and ADH into the vasculature.
The anterior pituitary gland- its an endocrine organs, it receives info via vascular connection
Look at slide 23 for all its hormones
Feedback
What are the different kinds of negative feedback
Based on distance travelled:
- long loop feedback
- short-loop feedback
- ultra-short loop feedback
Calcium example of negative feedback
Low plasma Ca2+ levels stimulate secretion of parathyroid hormone from parathyroid glands.
- the hormone acts on various tissues to increase plasma Ca2+ concentrations
- the increase is Ca2+ concentration acts as a negative feedback signal and shifts off the pathway.
Insulin example
High blood glucose, beta cells secretes insulin and cells increase uptake of glucose, which means blood glucose decreases ➡ negative feedback. Don’t have high blood glucose anymore so shut down production of insulin
Cortisol example
Stress, neural signal to hypothalamus, so it secretes corticotrophic releasing hormone, filters to anterior pituitary gland which triggers release of adrenocorticotropic hormones, which goes to adrenal cortex which stimulates production of cortisol. Cortisol increases amount of available energy so they can be in flight. Cortisol feedback into negative feedback
