A role for somatomedin C as a differentiating hormone and amplifier of hormone action on ovarian cells: studies with synthetically pure human somatomedin C and swine granulosa cells

Isolated swine granulosa cells incubated in chemically defined medium in vitro responded to synthetically pure human somatomedin C/IGF-I in a dose and time-dependent fashion with increased pregnenolone, progesterone and estradiol biosynthesis. These stimulatory actions were not mimicked by growth hormone, proinsulin, desoctapeptide insulin, epidermal growth factor, or fibroblast growth factor. Moreover, somatomedin C/IGF-I augmented the steroidogenic response of granulosa cells to exogenously supplied sterol substrate in the form of low-density lipoprotein, and amplified the stimulatory actions of the classical ovarian effector hormones, estradiol and follicle-stimulating hormone, in a synergistic fashion. The ability of somatomedin C/IGF-I to stimulate estradiol production on the one hand, and to act synergistically with estradiol to stimulate progesterone biosynthesis on the other hand, suggests a unique intrafollicular mechanism for amplifying progestin biosynthetic capacity in granulosa cells.     

Immunoreactive met-enkephalin in the canine adrenal; response to acute hypovolemic stress

Immunoreactive met-enkephalin was measured in the adrenal, kidney, liver, and intestine of the dog using radioimmunoassay. Adrenal tissue concentrations were 20 to 200-fold higher than the other tissues studied. In response to acute hypovolemic stress, the concentration of met-enkephalin in the adrenal vein of the dog increased 6-fold over basal peripheral arterial levels. These results suggest that the canine adrenal gland is a rich source of this opioid peptide and that the adrenal releases met-enkephalin in response to acute stress.     

Arthrite rhumatoide traitée par noréthynodrel associée à mestranol: Aspects cliniques et tests de laboratoire

A cause de l''effet favorable de la grossesse sur l''activité de l''arthrite rhumatoïde, on s''est demandé si une pseudo-grossesse, produite par un progestatif de synthèse n''entraînerait pas une rémission du moins partielle de cette maladie.Noréthynodrel associée à mestranol (Enovid), 30 mg./jour, a été administrée à 44 femmes pendant quatre à 24 mois. A cause d''effets secondaires indésirables, 11 patientes furent soustraites de l''investigation. Les résultats s''appuient sur 33 cas. Une rémission apparente complète s''est manifestée chez sept patientes aux stades précoces de la maladie; chez 15, une amélioration objective des signes inflammatoires a été observée; chez quatre, une amélioration subjective seule a été notée; chez sept, il n''y a eu aucune amélioration. Dix-sept femmes sur 36 ont présenté une altération d''un ou plusieurs tests hépatiques. Trois présentèrent un ictère cholestatique. Les 17-OH plasmatiques se sont élevés à trois ou quatre fois la normale.De cette étude il ressort que noréthynodrel associée à mestranol peut produire une atténuation des signes inflammatoires de l''arthrite rhumatoïde. L''effet est palliatif, mitigé et non curatif et ne résulte pas nécessairement de l''état de pseudo-grossesse en soi.     

Size-related photosynthetic characteristics of phytoplankton during periods of seasonal mixing and stratification in an oligotrophic multibasin lake system

Phytoplankton photosynthetic responses were studied in two basinsof an oligotrophic lake (Québec, Canada). which are characterizedby the absence (shallow Basin 1) and presence (deeper Basin2) of seasonal thermal stratification. Size-fractionated photosynthesiswas used to characterize changes in phytoplankton characteristicsduring periods of seasonal mixing and stratification. Seasonalvariations of P _max showed size-related differences, with maximumvalues in July for the picoplankton and in November for thenanoplankton. Similar patterns of variability in     

The efficacy of CGS 20267 in suppressing estrogen biosynthesis in patients with advanced stage breast cancer

The pharmacologic inhibition of aromatase activity has been the focus of clinical trials in patients with advanced stage breast cancer. Recent developments with imidazole compounds that inhibit aromatase activity suggest their clinical use as potent inhibitors of estrogen biosynthesis in postmenopausal breast cancer patients. In this Phase I, open-label, dose-range finding study, we examined the inhibitory potency of CGS 20267 on blood and urine levels of estradiol, estrone and estrone sulfate in 8 patients with metastatic breast cancer. Studies included evaluation of adrenal and thyroid function to look for evidence of general hydroxylase inhibition at dose levels effective for aromatase blockade. Patients were administered CGS 20267 at doses of 0.1 and 0.25 mg, once a day in ascending doses over a 12-week period. Preliminary data reveal that CGS 20267 elicits a striking suppression in plasma estradiol, estrone and estrone sulphate which was observed in some patients as quickly as within 24 h of the first dose. Estrogen suppression of over 90% was achieved within 2 weeks of therapy. No alterations in either baseline or ACTH (cortrosyn) stimulated cortisol and aldosterone levels were observed through the 12 weeks of therapy. In addition, 24 h urine sodium and potassium values were not appreciably altered during therapy. We conclude that CGS 20267 is a potent, specific inhibitor of estrogen biosynthesis in postmenopausal patients with metastatic breast cancer and effectively reduces blood and urine estrogens to undetectable levels.     

Phenotypic features of breast cancer cells overexpressing ornithine-decarboxylase

Polyamines (PA) have been shown to be critical mediators of estradiol-induced breast cancer cell proliferation. This finding suggests that constitutive activation of the PA pathway may promote tumor progression, possibly leading to hormone independence. To test this hypothesis, we transfected hormone-responsive MCF-7 breast cancer cells with a complementary DNA coding for ornithine-decarboxylase (ODC), the first rate-limiting enzyme in PA biosynthesis. Marked ODC over-expression observed in stably transfected clones was associated with a selective increase in cellular putrescine content, while spermidine and spermine levels were not altered. ODC-overexpressing MCF-7 cells were resistant to the antiproliferative effects of low but not high concentrations of the enzyme inhibitor, α-difluoromethylornithine. In agreement with our hypothesis, sensitivity to the growth-promoting action of estradiol was reduced by approximately one third (P < 0.001) in ODC-overexpressing MCF-7 cells compared with vector-only transfected clones. Basal growth under anchorage-dependent conditions was only marginally increased by ODC overexpression (P = 0.048), while clonogenicity in soft agar was actually reduced. These data suggest that activation of PA biosynthesis may contribute in part to the acquisition of estrogen independence by breast cancer cells. Since only putrescine content was increased as a result of ODC overexpression, these data may underestimate the overall influence of the PA pathway on breast cancer phenotype. © 1995 Wiley-Liss, Inc.     

The E6 and E7 genes of human papillomavirus type 6 have weak immortalizing activity in human epithelial cells.

Previous studies have shown that the E7 gene of human papillomavirus (HPV) type 16 or 18 alone was sufficient for immortalization of human foreskin epithelial cells (HFE) and that the efficiency was increased in cooperation with the respective E6 gene, whereas the HPV6 E6 or E7 gene was not active in HFE. To detect weak immortalizing activities of the HPV6 genes, cells were infected with recombinant retroviruses containing HPV genes, alone and in homologous and heterologous combinations. The HPV6 genes, alone or together (HPV6 E6 plus HPV6 E7), were not able to immortalize cells. However the HPV6 E6 gene, in concert with HPV16 E7, increased the frequency of immortalization threefold over that obtained with HPV16 E7 alone. Interestingly, 6 of 20 clones containing the HPV16 E6 gene and the HPV6 E7 gene were immortalized, whereas neither gene alone was sufficient. Thus, the HPV6 E6 and E7 genes have weak immortalizing activities which can be detected in cooperation with the more active transforming genes of HPV16. Acute expression of the HPV6 and HPV16 E6 and E7 genes revealed that only HPV16 E7 was able to stimulate the proliferation of cells in organotypic culture, resulting in increased expression of the proliferative cell nuclear antigen and the formation of a disorganized epithelial layer. Additionally, combinations of genes that immortalized HFE cells (HPV16 E6 plus HPV16 E7, HPV16 E6 plus HPV6 E7, and HPV6 E6 plus HPV16 E7) also stimulated proliferation.     

Alpha-1,4-glucosidase activity in ram seminal plasma is inversely related to serum testosterone

The epididymis of adult rams is the primary source of alpha-glucosidase in seminal plasma. Two breeds of rams were selected to ascertain whether the enzyme was under androgenic control during adult life of rams. Opposite variations between serum testosterone and alpha-glucosidase were recorded over a period of 16 months in Suffolk and Finnish Landrace. In addition, the highest percentage of sperm motility was associated with a low alpha-glucosidase content of seminal plasma. Data from this study suggest that seasonal variations of testosterone in adult rams exert a negative control on the presence of alpha-glucosidase in semen.