Immunohistochemical localization of sex hormone-binding globulin in normal and neoplastic breast tissue.

The distribution of sex hormone-binding globulin-like antigens (SHBG-LA) in normal and neoplastic human breast tissues was investigated by immunohistochemistry, employing a monospecific polyclonal antiserum against highly purified human SHBG and an avidin-biotin-peroxidase complex (ABC) method in formalin-fixed paraffin embedded tissue sections. In normal breast tissues the staining of SHBG-LA was present exclusively in the cytoplasm of epithelial cells of ductal and ductular types. Nuclei as well as stromal and lymphatic tissues remained unstained. While the staining was positive in all cases of intraductal carcinoma, only 4 out of 15 infiltrating carcinomas revealed SHBG-LA. The demonstration of a plasma sex steroid binding globulin in the cytoplasm of endocrine target cells is consistent with the hypothesis that steroid-binding globulins are able to enter target cells. The apparent loss of this specific cell function in infiltrating carcinomas may result from dedifferentiation and change of cell membrane properties occurring during the process of neoplastic progression.     

Adipose tissue. Pathophysiology, distribution, sex differences and the role in inflammation and cancerogenesis

The role of adipose tissue is energy storage, but there is increasing evidence that adipocytes and adipokines are involved in metabolic and inflammatory processes. This paper reviews the pathophysiology of different adipose tissue depots. Interrelationships between sex hormones, adipose tissue and risk factors are also discussed. Present study focuses on the effects of adipokines on immune system and on the mechanisms relating adiposity to cancer risk.     

Evolution of sex I. Primitive sex

Sex is a process of fusion of separate hereditary determinants. The advantages which could accrue from such fusions are protection against deleterious mutations and the possibility of combining favorable alleles into a single individual. If the fitness of the aggregate resulting from fusion is greater than its parts there will be strong selective pressure to perpetuate the aggregate in all progeny. Continued fusion presents problems though and new environmental conditions may occur which favor segregation. Segregation is also favored because of the existence of favorable recessive mutations. It is argued that the balance between these alternative goals of phenotype stability versus variety achieved an effective compromise with the development of the meiosis-fusion-mitosis cycle.     

A new approach to study the sex differences in adipose tissue

Obesity is one of the most invaliding and preventable diseases in the United States. Growing evidence suggests that there are sex differences in obesity in human and experimental animals. However, the specific mechanisms of this disease are unknown. Consequently, there is any particular treatment according to the sex/gender at this time. During the last decade, we observe a rise in the study of adipocyte and the possible mechanisms involved in the different roles of the fat. Furthermore, the effect of sex steroids on the adipocyte is one of the fields that need elucidation. Supporting evidence suggests that sex steroids play an essential role not only in the fat distribution, but also, in its metabolism, proliferation, and function. Thus, using in vitro and in vivo studies will contribute to our fight against this critical health public problem encompassing both sexes. In the present review, we discuss some of the recent advances in the adipocytes and the effect of the sex steroids on the adipose tissue. Also, we propose a new alternative to study the role of sex steroids on adipocyte biology through human adipose-derived stem cells.     

Variation in tissue carnitine concentrations with age and sex in the rat

Diabetes, starvation and various hormonal treatments are known to alter drastically carnitine concentrations in the body. Before the mechanisms controlling carnitine metabolism could be determined, it was necessary to establish normal carnitine concentrations in both sexes at different ages. Carnitine was assayed in plasma, liver, heart and skeletal muscle of rats from birth to weaning. The plasma carnitine increased rapidly during the first 2 days after birth. Carnitine in both heart and skeletal muscle increased, whereas liver concentrations declined during the first week of life. A carnitine-free diet containing sufficient precursors for carnitine biosynthesis was fed to weanling rats. Groups of ten male and ten female rats were killed each week for 10 consecutive weeks. Carnitine was determined in plasma, liver, heart, skeletal muscle, urine and epididymis in the male. There was no difference in carnitine concentrations between the sexes at weaning. Plasma, heart and muscle concentrations were higher in adult male rats than in adult females. However, liver carnitine and urinary carnitine concentrations were higher in adult female than in adult male rats. The epididymal carnitine concentration increased very rapidly during 50 to 70 days of age and the differences in carnitine concentrations between the sexes also became apparent during this time. Thus both the age and the sex of the human subject or experimental animal must be considered when investigating carnitine metabolism.     

Electron microscopic identification of sex chromatin bodies of tissue culture cells

Summary A method is described for the unequivocal identification of sex chromatin bodies in electron micrographs of thin sections of tissue culture cells derived from human skin. Fibers, rodlets, and circular profiles having a similar diameter of about 200 Å appear to be the only components of the sex chromatin bodies. The fibers and rodlets are sometimes resolvable into two similar subunits and the circular profiles often have a less electron dense center. The overall density of sex chromatin bodies is found to be considerably less than that of metaphase chromosomes. The fibers of the sex chromatin bodies found lying away from the nuclear periphery appear to be organized more compactly than the fibers of the sex chromatin bodies found lying at the nuclear periphery.This paper is based on investigations supported by a research grant No. GM-04738 from the National Institutes of Health, Public Health Service, to Dr. H. Ris, Department of Zoology, University of Wisconsin.     

The role of sex hormones in the growth of antler bone tissue. I: Endocrine and metabolic effects of antiandrogen therapy.

Cyproterone acetate (CA), an antiandrogenic compound, was used in order to investigate the role of testosterone in bone growth processes. The formation of Haversian systems in the growing antlers of white-tailed deer (Odocoileus virginianus) were substantially affected by only 3.5 mg of CA kg/wk. The mineralization processes of the bone matrix were almost completely blocked and the antlers persisted in growing throughout the whole year. Plasma levels of thyroxine, alkaline phosphatase and GH were higher while cortisol and testosterone levels were lower than in controls. No differences were registered in plasma levels of Ca, P or urea nitrogen. Despite hypertrophy of interstitial tissue, spermatogenesis was almost completely blocked. The sexual behaviour and the body appearance of experimental animals was typical for castrates.     

Trisomy 7 and sex chromosome loss in human brain tissue

Short-term cultures of nonneoplastic brain tissue from 11 patients, seven of whom had a malignant brain tumor, were cytogenetically examined. In only a single case was a wholly normal chromosome complement detected; the remaining ten cases exhibited mosaicism with clonal numerical aberrations found alongside cells carrying a normal karyotype. The abnormal clones were characterized by trisomy 7, the loss of the Y chromosome in men and an X chromosome in women, or by combinations thereof. No structural aberrations were present. Our findings demonstrate that although -Y, -X, and +7 have in the past repeatedly been associated with brain tumors, these changes presumably reflect normal in vivo organ mosaicism and, thus, should not be accepted as neoplasia-specific in this context.     

Influence of sex and sex hormones on transplantable hepatocellular carcinoma in the rat.

Palpable subcutaneous transplants of hepatocellular carcinoma-35 appeared slightly earlier in male animals; however, the number of successful growths was no greater than that in female animals. Castration and administration of testosterone or diethylstilbestrol were performed after the transplants reached 1.0-1.5 cm in size. The carcinoma was less well differentiated histologically, had more bile pigment, grew rapidly, mestastasized sooner and killed the host quickly in castrated females given testosterone propionate. Bile was present in lung metastases. There was little difference in the growth rate in intact or castrated male or female animals. Exogenous diethylstilbestrol slowed the growth of the transplants and cause weight loss in castrated males. The weight loss was felt to be related to extensive necrosis of the carcinoma.     

On the origin of meiosis and sex.

The pre-karyote (the host for alpha-proteobacteria) is not assumed to have had a fusion prohibiting cell surface, and thus unlike prokaryotes could have practiced sex. A single DNA damage checkpoint control might have been the only checkpoint pathway regulating the ancient pre-karyotic cell cycle from which the modern eukaryotic cell cycle evolved. This single checkpoint would allow the cell division only when all the pre-karyote genome was completely replicated without mistakes. If the restart of DNA replication was impossible after DNA damage, the last chance to survive for this in S-phase blocked pre-karyote would be the fusion with the partner. After the fusion, recombination, and subsequent completing the replication of both haploid sets, the single DNA damage checkpoint would allow two subsequent rounds of fission. The fusion might have represented both useful repair strategy, and a mechanism of horizontal transmission of the ancestors of mitochondria. The presence/absence of these symbionts might have been a primordial form of sexual determination.