Adrenal Embryonic development

In addition to Its structural role In membranes, discussed In Chapter 5, cholesterol Is the precursor for several Important bloactive molecules. They Include bile acids (see Figure 18-6), which are made In the liver and help emulsify dietary fats for digestion and absorption In the Intestines, steroid hormones produced by endocrine cells (e.g., adrenal gland, ovary, testes), and vitamin D produced In the skin and kidneys. Arthropods need cholesterol or other sterols to produce membranes and ecdysterold hormones, which control development however, they cannot make the precursor sterols themselves and must obtain these compounds In their diet. Another critical function of cholesterol Is Its covalent addition to Hedgehog protein, a key signaling molecule In embryonic development (Chapter 15). 

In contrast to the other P450 family 26 P450s, P450 26C1 appears to be expressed mainly dirr-ing embryonic development, at least in animal models [2509]. Sites of expression include hindbrain, inner ear, first bronchial arch, tooth buds, and eqttatorial retina (of mice) [2533, 2534] However, low levels (of mRNA) can be detected in adult adrenal gland, lung, spleen, testis, and brain [2509, 2535]. Expression is also seen in keratinocyte cell lines treated with 9-cis- or all-irans-retinoic acid [2509]. 

CYP1B1 is also expressed in the fetus in multiple tissues, particularly in thymus, spleen, kidney, and adrenal. A null CYP1B1 phenotype in humans has been associated with appearance of primary congenital glaucoma. Consistent with an important endogenous role for this enzyme in development of the eye, CYP1B1—which, in addition to biotransformation of xenobiotics, is also capable of metabolizing retinoid and sex steroids—is expressed in embryonic ocular tissues. 

Alginate-polylysine has been used to encapsulate hepatocytes (32-34), parathyroid cells (35) and growth hormone transfected fibroblasts (36). Poly (acryl-onitrile/vinyl chloride) (PAN/PVC) macrocapsules have been used with PC12 (37, 38), embryonic mesencephalon tissue (39), thymic epithelial cells (40), adrenal chromaffin cells (41) and islets (25) using preformed hollow fibers or more recently coextrusion techniques (41) similar to those we have developed microcapsules cannot be made since DMSO is used as the solvent. All these studies have concluded from the maintenance of viability of the islets or cells that immunoprotection provided by the capsule membrane was compatible with... 

The development of the various adrenal enzymes in the fetal adrenal may also be of considerable significance in interpreting the lack of activity observed after birth. jS-Hydroxysteroid dehydrogenase is low in fetal liver thus, the pathway prevails (pregnenolone— dehydroepiandrosterone), and cortisol synthesis is low. The relatively large adrenals found in utero may result from compensatory hyperplasia in response to low cortisol secretion. In early embryonic life, 21- and 11-hydroxylase activities are low, but they increase with the age of the fetus. 

A controversial topic, the sulgect of much debate on medical, political, and religious grounds, is embryonic stem cell research. These cells, derived from early embryos, have the potential to develop into any oi n within the human body. For example, in theory, a diabetic could grow a new pancreas, which would produce insulin. Proponents of stem cell research allude to a future in which a patient could grow a new adrenal gland, a paraplegic could walk... 

It is important to note that embryonic mouse intestine contains a protein lacking alkaline phosphatase activity which cross-reacts with antibody against intestinal alkaline phosphatase. Under the influence of corti-coid hormones from the developing adrenal, this enzymically inactive protein is converted to active alkaline phosphatase (Etzler and Moog, 1966,1968). 

There is particular concern that the pharmacodynamic activities of some drugs may be expressed in consumers, and this concern has been paramount over the presence of hormonally active substances, and particularly those with the capacity to act as endocrine disrupters in humans or indeed, in environmental organisms. There is a considerable body of concerns that include adverse effects on sexual, thyroid, adrenal and reproductive function in humans and other animals, as well as genital abnormalities e.g. hypospadias) and effects on embryonic and foetal development. This has led to the tighter regulation of human pharmaceutical products in a number of countries from the point of view of environmental effects and environmental assess-... 

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