An essential requirement for hormone action is the presence of a functional receptor. If the receptor is lost, the same symptoms as hormone loss will occur. The pathways involved in hormone action are complex and involve various intracellular messengers and effector proteins. Abnormal expression or activity of any of these components can lead to endocrine diseases. Hormonal signals can be terminated through processes such as hormone/receptor internalization, phosphorylation/dephosphorylation, proteosomal destruction of the receptor, and generation of feedback inhibitors.

Endocrine diseases can be broadly categorized as hyperfunction or hypofunction of a specific hormonal pathway. Hypofunction can be caused by a lack of active hormone or hormone resistance due to inactivation of hormone receptors or post-receptor defects. Testicular feminization syndrome is an example of hormone resistance where the androgen receptor is mutated and cannot be activated by androgens. If the diagnosis is not made before puberty, the testis becomes hyperstimulated due to the disruption of negative feedback between the testis and the pituitary gland, resulting in increased androgen levels.

Endocrine signaling involves the regulated secretion of hormones into the extracellular fluid, diffusion of hormones into the vasculature and circulation throughout the body, and binding of the hormone to a specific receptor within cells of the target organ.

The endocrine system is comprised of the endocrine tissue of various organs, including the pancreas, parathyroid glands, pituitary gland, thyroid gland, adrenal glands, and gonads (testes or ovaries).

Negative feedback plays a crucial role in maintaining stability in endocrine systems. Hormonal rhythms are regulated by negative feedback loops.

Protein/peptide hormones are produced on ribosomes and stored in membrane-bound secretory granules. They do not have a direct biological effect as a result of receptor defects. However, androgens are peripherally converted to estrogens, leading to a feminized external phenotype, female sexual identity, and usually a sexual preference for men in affected individuals who are genetically male (i.e., 46,XY). Treatment involves the removal of hyperstimulated testes, estrogen replacement therapy, and counseling for the patient and their partner/spouse to address infertility and social/psychological distress.

Protein/peptide hormones do not readily cross cell membranes and act through cell membrane-associated receptors.

Catecholamines are synthesized in the cytosol and secretory granules and also do not easily cross cell membranes. They act through cell membrane-associated receptors.

Steroid hormones are not stored in tissues and can readily cross cell membranes. They act through intracellular receptors.

Thyroid hormones are synthesized in follicular cells and stored as thyroglobulin in follicular colloid. They can cross cell membranes and associate with nuclear receptors.

Some hormones exert their effects through membrane receptors, and their responses are mediated by rapid intracellular signaling pathways.
The presence of a functional receptor is an absolute requirement for hormone action, and loss of a receptor produces essentially the same symptoms as loss of hormone. In addition to the receptor, there are fairly complex pathways involving numerous intracellular messengers and effector proteins. Accordingly, endocrine diseases can arise from abnormal expression or abnormal activity, or both, of any of these signal transduction pathway components. Finally, hormonal signals can be terminated in several ways, including hormone/receptor internalization, phosphorylation/ dephosphorylation, proteosomal destruction of receptor, and generation of feedback inhibitors.
Endocrinediseasescanbebroadlycategorizedashyperfunctionorhypofunctionofaspecifichormonalpathway.Hypofunctioncanbecausedbylackofactivehormoneorbyhormone resistance asaresultofinactivationofhormonereceptorsorpostreceptordefects.Testicular feminization syndrome isadramaticformofhormoneresistanceinwhichtheandrogenreceptorismutatedandcannotbeactivatedbyandrogens.Inpatientsinwhomthediagnosisisnotmadebeforepuberty,thetestisbecomeshyperstimulatedbecauseofabrogationofthenegativefeedbackbetweenthetestisandthepituitarygland.Theincreasedandrogenlevels 1.
Endocrine signaling involves (1) regulated secretion of an extracellular signaling molecule, called a hormone, into the extracellular fluid; (2) diffusion of the hormone into the vasculature and circulation throughout the body; and (3) diffusion of the hormone out of the vascular compartment into the extracellular space and binding to a specific receptor within cells of a target organ.
2.
The endocrine system is composed of the endocrine tissue of the pancreas, the parathyroid glands, the pituitary gland, the thyroid gland, the adrenal glands, and the gonads (testes or ovaries).
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Negative feedback represents an important control mechanism that confers stability on endocrine systems. Hormonal rhythms are imposed on negative feedback loops.
4.
Protein/peptide hormones are produced on ribosomes and stored in endocrine cells in membrane-bound secretory granules. They typically do not cross cell
Bae YJ, Kratzsch J. Corticosteroid-binding globulin: modulating mechanisms of bioavailability of cortisol and its clinical implications. Best Pract Res Clin Endocrinol Metab. 2015;29:761-772.
havenodirectbiologicaleffectasaresultofthereceptordefect.However,theandrogensareperipherallyconvertedtoestrogens.Thusaffectedindividualsaregeneticallymale(i.e.,46,XY)buthaveastronglyfeminizedexternalphenotype,afemalesexualidentity,andusuallyasexualpreferenceformen(i.e.,heterosexualinrelationtosexualidentity).Treatmentinvolvesremovalofthehyperstimulatedtestes(whichresideintheabdomenandposeariskforcancer),estrogenreplacementtherapy,andcounselingforthepatientand,ifoneexists,thepartner/spousetoaddressinfertilityandsocial/psychologicaldistress.
membranes readily and act through cell membrane– associated receptors.
5.
Catecholamines are synthesized in the cytosol and secretory granules and do not readily cross cell membranes. They act through cell membrane– associated receptors.
6.
Steroid hormones are not stored in tissues and generally cross cell membranes relatively readily. They act through intracellular receptors.
7.
Thyroid hormones are synthesized in follicular cells and stored in follicular colloid as thyroglobulin. They cross cell membranes and associate with nuclear receptors.
8.
Some hormones act through membrane receptors, and their responses are mediated by rapid intracellular signaling pathways.
9.