Lecture 10: Biosynthesis of Steroid Hormones Flashcards
modes of cell-cell communication
-juxtacrine signaling
-endocrine signaling
-paracrine signaling
-synaptic/neuronal signaling
-autocrine signaling
Juxtacrine signaling
-direct physical contact
Endocrine signaling
-travels far through blood to target organ
-low concentration
-high affinity receptors
-minutes to hours
Paracrine signaling
-travels short distance
-affects neighboring cells
-rapid and localized communication
synaptic/neuronal signaling
-neurotransmitter
-short distance
-high local concentration
-dissociate rapidly
-millisecond termination
autocrine signaling
-made and functions in same cell
Steroid hormone structure
-made from cholesterol
-planar, rigid, hydrophobic
-tight binding to receptors
-low concentrations in body
-bound to serum carrier proteins
Steroid hormone action
-diffuse through cell membrane
-bind steroid hormone receptor
-regulate transcription of a specific set of genes
Classes of steroid hormones
-sex and progestational hormones
-adrenocortical hormones
sex and progestational hormones
-progesterone
-17B-estradiol
-testosterone
Adrenocortical hormones
-Cortisol
-Aldosterone
structure of steroid hormones
-share 4 rings of cholesterol
Steroid receptors
-intracellular
-bind steroid hormones
-regulate transcription of specific set of genes
-belong to nuclear family
Steroid receptor structure
-DNA-binding domain
-hormone-binding domain
Hormone Responsive Elements (HRE)
-specific DNA seq
-binds to active, dimerized steroid receptors
-binds DNA-binding domain
-alters rate of transcription
negative feedback loop?
slide 15?
Synthesis of steroid hormones
-Cholesterol to pregnenolone
-P450
Pregnenolone to Aldosterone
-Pregnenolone to progeterone
-progesterone to aldosterone (ADRENAL)
Pregnenolone to DHEA
-17a-hydroxylase (adds -OH)
-17,20-Lyase (=O)
I’m not writing all those down
SLide 17 like actually
17a-hydroxylase deficiency
-rare form of congenital adrenal hyperplasia
-mutations in CYP17A1
-overproduction of mineralcoricoids
-deficiency of corticosteroids and sex hormones
17a-hydroxylase symptoms
-HYPOcortisolism (enlargement of adrenal glands)
-ambiguous genitalia
-hyperaldosteronism (HTN)
21-hydroxylase
-adds -OH to methyl on progesterone
21-hydroxylase deficiency
-major form of congenital adrenal hyperplasia
-mutations in CYP21A2
21-hydroxylase deficiency symptoms
-hypocorisolism
-hypoaldosteronism (hyponatremia can be life threating in infants)
21-hydroxylase deficiency premature androgen exposure
-ambiguous genitalia in female
-hirsutism
-early epiphyseal closure = short height
Synthesis of testosrerone and estradiol location
-ovaries and testes
-androstenedione too testosterone
-testosterone to 17B-estradiol
-17,20-Lyase
Transport of steroids
-by plasma proteins in plasma
-corticod-binding globulin (transcortin)
-sex hormone binding globuling (SHBG)
corticoid-binding globulin (transcortin)
-transport glucocorticoids and progesterone
sex hormone binding globulin (SHBG)
-transport testosterone and estradiol
Steroid metabolism
-in liver
-oxidation, sulfation, gglucoronidation to soluble forms
Steroid excretion
-in bile (estrogen)
-in urine (progesterone, androgen, glucocorticoids)
Aminoglutethimide
-inhibits aromatase and P450scc
-used to block steroid production in some hormone-dependent tumors (breat/prostate)
Ketoconazole
-antifungal at lower concentrations (block ergosterol synthesis)
-inhibits P450scc, 17a-hydroxylase, and 11B-hydroxylase
-can treat hyperglucocorticoid states (cushing’s syndrome)
-may cause toxic side effects
nonselective steroidgenesis inhibitor drugs
-aminoglutethimide
-ketoconazole
