This association changes physiochemical properties of the membrane; activating membrane proteins, altering cellular functions and ultimately influencing cation transport through the plasma membrane and stimulating the proton leak across the inner mitochondrial membrane. Hindered oxidative phosphorylation compromises ATP production, a major energy source for cellular energy metabolism and immune function. In vivo studies of Con-A stimulated thymocytes (in rats) and human immune cells that were administered high doses of methylprednisolone has been shown to inhibit respiration in a dose-dependent manner, inhibit plasma calcium and sodium uptake, and increase cytoplasmic calcium concentration. The summative process is as follows: Methylprednisolone intercalates in the plasma membrane, causes physiochemical changes, activates membrane proteins that inhibit plasma calcium and sodium uptake (mimicking an energy deficit state). ATP consumption drops (resembled by inhibited respiration), resulting in protein permeability at the inner mitochondrial membrane and uncoupling of oxidative phosphorylation. Of notable importance, DNA/RNA synthesis was not hindered. The dependency of house keeping cells and immune cells on ATP, results in immunosuppression during ATP deficit. Specific immune functions effected by this process are cytokinesis, migration, phagocytosis, antigen processing and presenting, antibody synthesis, cytotoxicity and regulation. The HPA axis
The activation of the hypothalamic-pituitary axis (HPA axis) stimulates the production of endogenous glucocorticoids within the adrenal cortex. The HPA axis interprets stimuli (stress, inflammation and circadian cues) and transduces a corresponding physiochemical response. Glucocorticoids released in the blood, serve as a messenger by binding to glucocorticoid receptors in a wide distribution across the body, including the HPA axis itself.
In the Dominican Republic, 5-alpha-reductase deficiency is not uncommon in the town of Las Salinas, resulting in social acceptance of the intersex trait. Men with the trait are called "güevedoces" (Spanish for "eggs at twelve"). 12 out of 13 families had one or more male family members that carried the gene. The overall incidence for the town was 1 in every 90 males were carriers, with other males either non-carriers or non-affected carriers. History
From early history, societies have been aware of intersex people. Some of the earliest evidence is found in mythology: the Greek historian Diodorus Siculus wrote of the mythological Hermaphroditus in the first century BC, who was "born with a physical body which is a combination of that of a man and that of a woman", and reputedly possessed supernatural properties. He also recounted the lives of Diophantus of Abae and Callon of Epidaurus. Ardhanarishvara, an androgynous composite form of male deity Shiva and female deity Parvati, originated in Kushan culture as far back as the first century AD. A statue depicting Ardhanarishvara is included in Indias Meenakshi Temple; this statue clearly shows both male and female bodily elements.Hippocrates (c. 460 – c. 370 BC Greek physician) and Galen (129 – c. 200/216 AD Roman physician, surgeon and philosopher) both viewed sex as a spectrum between men and women, with "many shades in between, including hermaphrodites, a perfect balance of male and female".