The primary hormonal products of the adrenal medulla are epinephrine and norepinephrine. Enzymatic modifications of the amino acid tyrosine give catecholamines their specificity. Catecholamines are stored in secretory vesicles along with adenosine triphosphate, Ca++, and chromogranins. Chromogranins play a role in the biogenesis of secretory vesicles and in their organization. Catecholamines circulate in blood either unbound or loosely bound to albumin. They produce their actions through cell membrane receptors because they cannot easily cross cell membranes. Catecholamines have short biological half-lives and are removed from blood primarily through cell uptake and enzymatic modification.

Steroid hormones are produced by the adrenal cortex, ovaries, testes, and placenta. These hormones belong to five categories: progestins, mineralocorticoids, glucocorticoids, androgens, and estrogens. Prohormones are converted to bioactive hormones through proteolytic cleavage by prohormone convertases. These convertases are expressed in a cell-specific manner. For example, insulin-producing cells express both PC1 and PC2. Proinsulin is cleaved from preproinsulin in the endoplasmic reticulum and packaged in secretory vesicles. Within the vesicle, PC1 and PC2 sequentially cleave a portion of the center of the single-chain connecting peptide. The mature secretory vesicle contains and secretes equimolar amounts of insulin and connecting peptide. Some prohormones contain the sequence of multiple hormones. Pituitary cells only express PC1 and release only ACTH. In contrast, certain neuronal cell types and keratinocytes express both PC1 and PC2 and can produce MSHs. There are also prohormones called polyproteins that contain multiple copies of the same bioactive peptide. For example, thyrotropin-releasing hormone is reiterated six times within the prepro-thyrotropin-releasing hormone sequence. Rare mutations in PC1 have been identified in humans and are associated with extreme childhood obesity, defects in glucose homeostasis, low glucocorticoid levels, loss of menstrual cycles and hypogonadism, and gastrointestinal problems.

Mineralocorticoids and glucocorticoids are 21-carbon steroids, while androgens are 19-carbon steroids and estrogens are 18-carbon steroids. The active metabolite of vitamin D is also considered a steroid hormone and is a secosteroid.
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).