DHEA has been determined to have medically significant activity and is the parent compound to the more active metabolites; 17α-AED, 17β-AED and 17β-AET, which exhibit strong biological activity that has been attributed to androgenic, estrogenic or anti-glucocorticoid activity in vivo and in vitro. This study compared DHEA, 17α-AED, 17β-AED and 17β-AET for their ability to activate the human AR, ER and GR receptors and determine the relative androgenicity, estrogenicity and glucocorticoid activity. The results show that, at the receptor level, these androstene hormones are weak AR and even weaker ER activators. Direct androstene hormone activation of the human AR, ERα, and ERβ may not be essential for their biological function. Similarly, these hormones indirectly activated the human GR receptor; only in the presence of high dexamethasone concentrations. These results underscore the major difference between androstene hormone interactions with these nuclear receptors. 17β-AED and 17α-AED, androstene epimers that produce either survival or death, were utilized to treat T98G Glioblastoma cells. We identified 26 genes oppositely regulated by 17β-AED and 17α-AED to directly affect the cellular life or death decision. Network analysis demonstrated that these 26 genes are essential to regulating three critical Glioblastoma pathways. This report, for the first time, demonstrates that naturally occurring, chemically identical adrenal hormones (17β-AED or 17α-AED) direct a cellular life or death decision through contrasting modulation of identical signaling pathways and core regulators. Chronic pressure ulcers represent a significant health problem and are characterized by hypoxia, bacterial infection, repetitive ischemia/reperfusion and altered cellular and systemic stress responses. Whole genome microarray analysis was utilized in conjunction with IPA® premiere networking software to analyze chronic wound edge tissue. IPA® network analysis identified Ubiquitin C (UBC) as the most significant network. Sixteen (16) ubiquitin C associated genes were identified to be different in the chronic pressure ulcer and normal skin control. Targeted network analysis associated core regulators to 8 UBC associated genes that are unique to chronic pressure ulcers. The identification of these genes will allow the establishment of more effective treatments for Spinal Cord Injury (SCI) patients with chronic pressure ulcers.

Steroids are important biological regulators existing in hormones which are used to control metabolism of the body. There are widespread applications in the pharmaceutical industry. Drugs of steroid nature - anti-inflammatory and antiallergic corticosteroids, diuretics, anabolics, androgens, gestagens, contraceptives, antitumor medications, etc. - are now widely used in human and veterinary medicine. Nowadays, biotechnological modifications of steroids are preferred over chemical modifications as a green chemistry since they are more likely to be natural. In this work four different Fusarium species were screened for bioconversion of steroids into pharmaceutically important derivatives of steroids by reduction, dehydrogenation, side-chain degradation etc. on A and D-rings containing many active sites. Fusarium spp. used in this work, namely Fusarium roseum OUT 4019, Fusarium anguioides OUT 4017, Fusarium bulbigenum OUT 4115 and Fusarium solani OUT 4021 are filamentous fungi, which belong to the class of Deuteromyces. They can grow using simple carbohydrates and nitrogen sources. 4-androstene-3,17-dione conversion is used as a model system. Under same environmental conditions it is found that whole cells of Fusarium roseum OUT 4019 can dehydrogenate at C-1 and C-2 producing androsta-1,4-diene-3,17-dione and also reduce at C-17 in addition to dehydrogenate at C-1 and C-2 producing 17-hydroxyandrosta- 1,4-dien-3-one, Fusarium anguioides OUT 4017 can reduce at C-17 producing 17-hydroxy-androst-4-en-3-one, Fusarium solani OUT 4021 can reduce at C-3 and C-17 producing androst-4-ene-3,17-diol at 25 C&deg / and 160 rpm with uncontrolled pH. In these conversions, androsta-1,4-diene-3,17-dione, 17-hydroxy-androsta-1,4-dien- 3-one, 17-hydroxy-androst-4-en-3-one, androst-4-ene-3,17-diol were isolated with 54 %, 22 %, 26 %, 90 % yields, respectively. In another study, bioconversion reactions of aromatic methyl ethers by Fusarium roseum OUT 4019 were investigated and for some compounds, cleavage of methyl ether was observed.

The accumulation of androstenone in the fat of mature boars results in boar taint; the conjugation of androstenone would decrease this important meat quality problem by decreasing the accumulation and increasing the excretion of androstenone. Leydig cells and testis microsomes from mature boars were incubated with radiolabeled pregnenolone, and the free and conjugated metabolites were examined by HPLC. Sulfated androstenone with a mass of 367 m/z was directly identified by MS, with a novel tentative structure of 3-keto-4- sulfoxy-androstenone. Addition of enolase to the microsomal incubations increased the formation of 3-keto-4-sulfoxy-androstenone. Overexpression of SULT2A1 in HEK cells resulted in the sulfoconjugation of dehydroepiandrosterone, but not androstenone, suggesting that SULT2A1 may not be involved in sulfoconjugation of androstenone. This thesis describes the novel direct characterization of androstenone sulfate and the importance of enolase in its formation. The relevance to boar taint metabolism is discussed.