Fig. 38.7 ). The primary hormonal products of the adrenal medulla are epinephrine and, to a lesser extent, norepinephrine. Catecholamines obtain their specificity through enzymatic modifications of the amino acid tyrosine. Catecholamines are stored in secretory vesicles that are part of the regulated secretory pathway. They are copackaged with adenosine triphosphate, Ca++, and proteins called chromogranins. Chromogranins play a role in the biogenesis of secretory vesicles and in the organization of components within the vesicles. Catecholamines are soluble in blood and circulate either unbound or loosely bound to albumin. They are similar to protein/peptide hormones in that they do not cross cell membranes readily and hence produce their actions through cell membrane receptors. Catecholamines have short biological half-lives (1 to 2 minutes) and are removed from blood primarily by cell uptake and enzymatic modification.
Steroid hormones are made by the adrenal cortex, ovaries, testes, and placenta. Steroid hormones from these glands belong to five categories: progestins, mineralocorticoids, glucocorticoids, androgens, and estrogens. Progestins,
Bioactivehormonesaregeneratedfromprohormonesthroughproteolyticcleavageoftheprohormonebyprohormone (alsocalledproprotein)convertases. Theseenzymesareexpressedinacell-specificmanner.Forexample,insulin-producingcells(betacells)ofthepancreaticisletsexpressbothPC1andPC2.Insulinisproducedaspreproinsulin,cleavedtoproinsulinintheendoplasmicreticulum,andpackagedinsecretoryvesiclesasproinsulin.Whileinthesecretoryvesicle,aportionofthecenterofthesinglechain(connectingpeptide)iscleavedsequentiallybyPC1andPC2.Thematuresecretoryvesiclecontainsandsecretesequimolaramountsofinsulinandconnectingpeptide.Sometimesprohormonescontainthesequenceofmultiplehormones.Forexample,theproteinproopiomelanocortin(POMC)containstheaminoacidsequencesofadrenocorticotropichormone(ACTH)andmelanocyte-stimulatinghormones(MSHs).PituitarycellsexpressonlyPC1andreleaseonlyACTHasabioactivepeptide.Incontrast,certainneuronalcelltypesandkeratinocytesexpressbothPC1andPC2andcanproduceMSHs.Therearealsoprohormones,calledpolyproteins, thatcontainmultiplecopiesofthesamebioactivepeptide.Forexample,thesequenceforthyrotropin-releasinghormoneisreiteratedsixtimeswithintheprepro–thyrotropin-releasinghormonesequence.RaremutationsinPC1havebeenidentifiedinhumansandareassociatedwithextremeobesityinchildhood,defectsinglucosehomeostasis,lowglucocorticoidlevels,lossofmenstrualcyclesandhypogonadism,andproblemsingastrointestinalfunction.
mineralocoricoids, and glucocorticoids are 21-carbon steroids, whereas androgens are 19-carbon steroids and estrogens are 18-carbon steroids (
Table 38.2 ). Steroid hormones also include the active metabolite of vitamin D (see ), which is a secosteroid (i.e., one of the rings has an open conformation).