Effects of Estrogen and Testosterone on Resting Energy Expenditure in Older Men

The mechanisms by which sex hormones cause changes in body composition are unclear. Sex steroid deficiency might directly reduce energy expenditure/fat oxidation and thereby predispose to increased body fat. Alternatively, sex steroid deficiency could result in lean tissue loss and thus reduced energy expenditure. Our objective was to examine the independent and combined effects of acute testosterone and estrogen withdrawal on respiratory exchange ratio (RER) and resting energy expenditure (REE) in men. The objective of the study was to examine the independent and combined effects of acute estrogen and testosterone withdrawal on RER and REE in men. A total of 54 men aged 50–80 years, BMI range of 17–35 kg/m² underwent a 3‐week eugonadal run‐in hormone‐treatment period involving suppression of endogenous sex steroids using letrozole and leuprolide acetate (Lupron) while sex steroid concentrations were maintained with transdermal testosterone (T) and estradiol (E). A second Lupron injection was then given and participants were randomized to one of the following four 3‐week treatment groups: group A (?T, ?E), group B (?T, +E), group C (+T, ?E), and group D (+T, +E). REE and RER were measured via indirect calorimetry before and after the 3‐week treatment period. Three‐week suppression and/or repletion of estrogen or testosterone did not produce changes in RER or REE within or between groups. We conclude that abrupt changes in sex steroids does not change resting substrate oxidation, indicating that changes that can be observed after more prolonged periods of deficiency are most likely due to direct effects of sex steroids on body composition.     

Redox Regulation of Transglutaminase 2 Activity

Transglutaminase 2 (TG2) in the extracellular matrix is largely inactive but is transiently activated upon certain types of inflammation and cell injury. The enzymatic activity of extracellular TG2 thus appears to be tightly regulated. As TG2 is known to be sensitive to changes in the redox environment, inactivation through oxidation presents a plausible mechanism. Using mass spectrometry, we have identified a redox-sensitive cysteine triad consisting of Cys²³⁰, Cys³⁷⁰, and Cys³⁷¹ that is involved in oxidative inactivation of TG2. Within this triad, Cys³⁷⁰ was found to participate in disulfide bonds with both Cys²³⁰ and its neighbor, Cys³⁷¹. Notably, Ca²⁺ was found to protect against formation of these disulfide bonds. To investigate the role of each cysteine residue, we created alanine mutants and found that Cys²³⁰ appears to promote oxidation and inactivation of TG2 by facilitating formation of Cys³⁷⁰–Cys³⁷¹ through formation of the Cys²³⁰–Cys³⁷⁰ disulfide bond. Although vicinal disulfide pairs are found in several transglutaminase isoforms, Cys²³⁰ is unique for TG2, suggesting that this residue acts as an isoform-specific redox sensor. Our findings suggest that oxidation is likely to influence the amount of active TG2 present in the extracellular environment.     

Female reproductive system and bone

The female reproductive system plays a major role in regulating the acquisition and loss of bone by the skeleton from menarche through senescence. Onset of gonadal sex steroid secretion at puberty is the major factor responsible for skeletal longitudinal and radial growth, as well as significant gain in bone density, until peak bone density is achieved in third decade of life. Gonadal sex steroids then help maintain peak bone density until menopause, including during the transient changes in skeletal mineral content associated with pregnancy and lactation. At menopause, decreased gonadal sex steroid production normally leads to rapid bone loss. The most rapid bone loss associated with decreased estrogen levels occurs in the first 8-10 years after menopause, with slower age-related bone loss occurring during later life. Age-related bone loss in women after the early menopausal phase of bone loss is caused by ongoing gonadal sex steroid deficiency, vitamin D deficiency, and secondary hyperparathyroidism. Other factors also contribute to age-related bone loss, including intrinsic defects in osteoblast function, impairment of the GH/IGF axis, reduced peak bone mass, age-associated sarcopenia, and various sporadic secondary causes. Further understanding of the relative contributions of the female reproductive system and each of the other factors to development and maintenance of the female skeleton, bone loss, and fracture risk will lead to improved approaches for prevention and treatment of osteoporosis.     

Investigations of the possible pharmacological effects of organotin(II) complexes

Antitumour, antifertility and histopathological investigations were carried out on male rats by the use of organotin complexes. The organotin complexes were synthesized by the alkylation of [Sn(TAML(n))Cl(2)] (n=1-4 and TAML(n) represents the tetraazamacrocyclic ligands) in the presence of CH(3)I or C(2)H(5)Br. The structures of all the complexes have been established on the basis of elemental analyses, conductivity measurements, IR, (1)H NMR, (13)C NMR, (119)Sn NMR and X-ray spectral data. The antitumour effect of the compounds was examined on swiss mice. The results obtained clearly indicated that the compounds, [C(2)H(5)Sn(TAML(3))C(5)H(5)N] and [C(2)H(5)Sn(TAML(4))C(5)H(5)N] display effective antitumour activity. The emphasis has been given on in vivo study on male albino rats (Rattus norvegicus) by performing serum analyses, blood analyses and fertility test.     

Biosynthesis of polyketides in heterologous hosts.

Polyketide natural products show great promise as medicinal agents. Typically the products of microbial secondary biosynthesis, polyketides are synthesized by an evolutionarily related but architecturally diverse family of multifunctional enzymes called polyketide synthases. A principal limitation for fundamental biochemical studies of these modular megasynthases, as well as for their applications in biotechnology, is the challenge associated with manipulating the natural microorganism that produces a polyketide of interest. To ameliorate this limitation, over the past decade several genetically amenable microbes have been developed as heterologous hosts for polyketide biosynthesis. Here we review the state of the art as well as the difficulties associated with heterologous polyketide production. In particular, we focus on two model hosts, Streptomyces coelicolor and Escherichia coli. Future directions for this relatively new but growing technological opportunity are also discussed.     

Mechanical response of reconstituted, freeze-dried collagen under compressive loads

The mechanical response under uniaxial compression of collagen discs, made from freeze-dried collagen reconstituted at acid pH, was investigated at 22, 29.5 and 35 degrees C. The pH during compression was maintained at the physiological level of 7.4. The fluid transport model developed by Bert (1970) was fitted to the data. Assumptions, made in the development of the model, were tested and the range of reliability of the model is discussed. The two fitting parameters of the model were found to be stronger functions of hydration than was previously reported. The compressive response of collagen was found to be only weakly influenced by temperature. At 35 degrees C there was evidence of thermal degradation. Some creep was noted at times greater than five half-times, but no attempt was made to quantify it.