Endocrinology 12 - Steroid Hormone Signalling All hormone action is receptor mediated Peptide - receptors will be on the cell surface Peptide hormones cannot cross the hydrophobic bilayer Steroid - receptor is inside the cell Structure - Cyclopentanoperhydrophenanthren (Sterane) structure o Four cyclic compounds o With a basic skeleton (androstane skeleton) . Three 6 carbon rings and one 5 carbon tings Side chain on c-17 position o Makes them lipophilic (dissolve in lipids) - All steroid hormones come from the pre-cursor; cholesterol - This cholesterol comes from two ways; o the cells making it; de novo synthesis " Start with acetyl COA > HMG-COA > Mevalonate > cholesterol · Mevalonate feeds into the cholesterol bio- synthesis pathway . The rate limiting step is between acetyl COA and HMG- CoA by HMG-CoA reductase . There is negative feedback at this step o Low-density lipoprotein breakdown (used to transport lipids around the body) · A complex consists of an outer phospholipid layer with a lipid rich core . Contains cholesterol . Breakdown of this complex, will release the cholesterol All steroid hormones are synthesised within the mitochondria 1. Cholesterol is actively transported into the mitochondria 2. Conversion of cholesterol into pregnenolone (all steroid hormones have this first step) a. The two enzymes critical for this step: i. Cholesteroldesmolase Cleaves the cholesterol at the c-17 position ii. Cytochrome P450 This cleavage event is facilitated by this All steroid hormones start with the same precursor, but the outcome is different based on the location the hormone is in the adrenal cortex Because of the enzymes that are involved in the synthesis are spatially restricted Hormonal Stimulation of Steroidogenesis e.g. ACTH is stimulated of cortisol synthesis - ACTH binds to the ACTH receptor on the surface - Activates Gs
- Ga-GTP recruits adenylate cyclase - adenylate cyclase converts ATP into cyclic AMP - CAMP then activates protein kinase A - protein kinase A stimulates cholesterol transporter - which moves the cholesterol required from the cytosol into the mitochondria Release - Steroid hormones are not like peptide hormones o They are not premade/packaged in secretory vesicles - Once they are synthesised, they are diffused into circulation - But they are lipophilic, so they reversibly bound to proteins in circulation Steroid Hormone Binding Proteins - Albumen o Bind two steroid hormones o Non-specifically o Low affinity - Steroid Hormone Binding Proteins o Specific o High affinity - Different classes of different hormones will utilise different binding proteins to keep them within the aqueous environment of circulation - Sex steroid binding protein o Testosterone o Estrodiol - Progesterone binding globulin o Progesterone - Corticosteroid binding protein o Cortisol o Aldosterone - This allows us to maintain an inactive pool of the hormone o Protects the hormone from any metabolic and chemical alteration o Allows us to have a pool of the hormones available should we need it . We can remove the interaction or increase . Therefore, we have a buffer against sudden changes in active hormone conc.