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Biomedical subjects

M S Weber

Publications and source records attributed to M S Weber.

10 recordsLinked to original sources
PubMed2000

Nutritional and somatotropin regulation of the mitogenic response of mammary cells to mammary tissue extracts.

Our objective was to investigate the mitogenic response of primary mammary epithelial cells to extracts of mammary parenchyma from 24 prepubertal Friesian heifers treated with placebo or growth hormone at either a low or a high feeding level. The mitogenic responses to mammary extracts were tested by using primary mammary epithelial organoids obtained from prepubertal heifers cultured for 4 to 5 d in collagen gels in serum-free medium supplemented to 5% concentration of the mammary extracts. Cell proliferation was determined using [methyl-3H]thymidine incorporation as a measure of DNA synthesis. High feeding level reduced DNA synthesis in response to mammary extracts. At low feeding level, growth hormone treatment decreased DNA synthesis in response to mammary extracts whereas, at high feeding level, growth hormone increased DNA synthesis in response to mammary extracts. These results suggest that locally produced growth factors are involved in the regulation of mammary development when mammary growth is modulated by feeding level and growth hormone treatment.

Animal Feed↗
PubMed2000

Regulation of local synthesis of insulin-like growth factor-I and binding proteins in mammary tissue.

Our objective was to investigate the mammary expression of insulin-like growth factor-I (IGF-I) and IGF-binding proteins in prepubertal heifers and regulation of IGF-I by bovine somatotropin (bST) and feeding level. Twenty-four prepubertal Friesian heifers were divided into six blocks according to genotype and starting date for the experiments. Within blocks, heifers were assigned to daily bST treatment (0 or 15 mg/d) at low or high feeding level (0.55 kg/d or 1.1 kg/d average daily gain, respectively) for 5 wk so that the mean body weight and standard error was approximately equal for all four treatment groups. At high feeding level, content of IGF-I protein in mammary tissue extracts was increased 46% by somatotropin compared with placebo. Somatotropin tended to increase abundance of IGF-binding protein-3 (40 to 43 kD) in mammary extracts. High feeding level increased abundance of a 24-kD binding protein and reduced abundance of IGF-binding protein-2 (32 kD) in mammary extracts. High feeding level reduced abundance of IGF-binding protein-1 mRNA in mammary tissue, but there was no significant effect of feeding level or somatotropin on mRNA levels of other IGF-binding proteins. These results suggest that effects of somatotropin treatment and feeding level on the prepubertal mammary gland are mediated in part by alterations in local synthesis of IGF-I and IGF-binding proteins.

Animals↗
PubMed1999

Growth hormone and mammary development.

Classic studies in rodents conducted in the 1950s showed that growth hormone (GH) is essential for mammary development both in the pubertal phase and during pregnancy. Since then, a considerable number of experiments have been carried out in ruminants to investigate the role of GH for regulation of normal mammary development and to examine the possibility of enhancing mammary growth by administration of GH. The available evidence demonstrates that GH treatment stimulates mammary growth before puberty, but the data do not convincingly support the idea that the effect is translated into increased milk yield. GH treatment during late pregnancy seems to stimulate both mammary growth and milk yield during lactation. The limited data concerning the effect of GH on mammary growth during lactation indicate that mammary growth is unaffected by GH treatment in early lactation, whereas GH seems to increase the amount of mammary parenchyma in mid-lactation. The mechanism of action of GH remains a puzzle, but the effect of exogenous GH most likely involves insulin-like growth factor-I (IGF-I). Full understanding of the role of endogenous GH for regulation of normal mammary development requires more knowledge about the interaction between GH and IGF-I and the interplay between the GH-IGF-I axis and locally produced factors, including receptors, binding proteins, and growth factors.

Animals↗
PubMed1999

Contribution of insulin-like growth factor (IGF)-I and IGF-binding protein-3 to mitogenic activity in bovine mammary extracts and serum.

Peripubertal development of the mammary gland is probably mediated by locally produced growth factors acting in concert with circulating mitogens. Our objective was to investigate the effect of recombinant human insulin-like growth factor-binding protein-3 (rhIGFBP-3) or insulin-like growth factor-I (IGF-I) antibodies on the IGF-I-related mitogenic activity of bovine serum and of mammary tissue extracts in primary mammary epithelial cell cultures. Cells were obtained from prepubertal female calf mammary tissue and cultured in three-dimensional collagen gels. An aqueous mammary parenchymal tissue extract (pooled from 20 prepubertal heifers) or serum (pooled from 3 heifers) at a concentration of 5% was added to the medium containing either rhIGFBP-3 or monoclonal or polyclonal antibodies to human IGF-I. Cell proliferation was evaluated using [methyl-3H]thymidine incorporation as a measure of DNA synthesis. Addition of mammary extracts stimulated DNA synthesis 545% compared with basal medium. Addition of serum stimulated DNA synthesis by 28%. Mitogenic activity of serum and added IGF-I was abolished by addition of rhIGFBP-3 in equimolar concentrations with IGF-I. For mammary extracts, mitogenic activity was inhibited by 35%, 50%, and 82% by the addition of rhIGFBP-3 at, respectively, 1, 2 and 4 times the molar IGF-I concentration in the extract. Addition of rhIGFBP-3 to basal medium reduced DNA synthesis by 26%, whereas IGF-I antibodies had no consistent effect. These results indicate that circulating and mammary-synthesized IGF-I and IGFBPs probably play a critical role in prepubertal development of the bovine mammary gland.

Analysis of Variance↗
PubMed1998

Expression of ovine insulin-like growth factor-1 (IGF-1) stimulates alveolar bud development in mammary glands of transgenic mice.

To determine whether murine mammary growth is modulated by local insulin-like growth factor-1 (IGF-1) production, expression of recombinant IGF-1 was directed to the mammary glands of transgenic mice using an ovine prepro IGF-1 cDNA under control of the mouse mammary tumor virus-long terminal repeat (MMTV-LTR) promoter. Bioactivity of recombinant IGF-1 in transgenic mouse milk extracts was demonstrated by a concentration-dependent increase in [3H]thymidine incorporation in clonal bovine mammary epithelial cells (MAC-T) compared with control mouse milk extracts; moreover, addition of excess recombinant human insulin-like growth factor binding protein-3 (rhlGFBP-3) abolished the increase in [3H]thymidine incorporation attributed to recombinant IGF-1 in transgenic mouse milk. Recombinant IGF-1 was produced in mammary tissue of virgin and pregnant transgenic mice, and secreted into milk of lactating mice. However, recombinant IGF-1 was not detected in serum from transgenic mice; and ligand blot analysis of serum insulin-like growth factor binding proteins (IGFBPs) indicated no differences owing to transgene presence. In peripubertal virgin mice at 49 d of age, the frequency of appearance of mammary alveolar buds was significantly higher in MMTV-IGF-1 than in CD-1 mice, and was unaffected by ovariectomy or estradiol treatment. In conclusion, mammary synthesis of recombinant IGF-1 enhances the rate of development of alveolar buds in mammary glands of virgin transgenic mice.

Animals↗
PubMed1991

Dopamine receptors in the ventral tegmental area affect motor, but not motivational or reflexive, components of copulation in male rats.

Microinjection of apomorphine into the ventral tegmental area (VTA) of male rats was previously shown to delay the onset of copulation and slow its rate, presumably by stimulating impulse-regulating autoreceptors on cell bodies of the A10 mesocorticolimbic dopamine tract. Such stimulation would be expected to slow the firing rate of these neurons and, thereby, to impair locomotion and/or motivational processes. The present experiments tested whether the delayed onset and slowed rate of copulation were related to deficits in motor performance, sexual motivation, and/or genital reflexes. In X-maze tests the speed of running to all 4 goal boxes was slowed; however, the percentage of trials on which the male chose the female's goal box was not decreased. Examination of videotaped copulation tests revealed that the male showed fewer complete copulatory behaviors (mounts, intromissions, and ejaculations), but more misdirected or incomplete copulatory attempts after apomorphine in the VTA. There were also fewer scores of active, as opposed to inactive, behaviors, and the onset and rate of copulation were slowed. The total number of female directed behaviors was not different in apomorphine tests, compared to vehicle. Finally, tests of ex copula genital reflexes revealed no significant effects of apomorphine in the VTA on erections, penile movements, or seminal emissions. These data suggest a role of the VTA in the motor aspects and/or sensorimotor integration of copulation. Sexual motivation and ex copula genital reflexes appeared to be unaffected by apomorphine in the VTA.

Animals↗
PubMed1990

Rotation of the anatomic regions used for insulin injections and day-to-day variability of plasma glucose in type I diabetic subjects.

Treatment of type I diabetes mellitus is hindered by the often large fluctuations in blood glucose concentration experienced by affected individuals. To determine to what extent day-to-day variation in blood glucose levels can be reduced if insulin is injected in the same anatomic region rather than in different regions using a rotational scheme, as is commonly recommended, 12 type I diabetic subjects were studied. Insulin injections were given in the abdomen for 3 days and rotated among arms, abdomen, and thighs for 3 days using a crossover design with random assignment of treatment order. Blood samples for measurement of plasma glucose levels were obtained at nine scheduled times on each day. Insulin dose, diet, and physical activity were held constant for each subject. During the abdominal injection period, the mean SD of plasma glucose levels and the mean variance of plasma glucose levels were both less at all nine time points than during the rotating injection period. Overall values for the SD of plasma glucose levels were 2.7 +/- 0.2 mmol/L for the abdominal injection period and 3.7 +/- 0.3 mmol/L for the rotating injection period. Overall values for the variance of plasma glucose levels were 9.2 +/- 1.4 mmol2/L2 for the abdominal injection period and 17.4 +/- 2.2 mmol2/L2 for the rotating injection period. We conclude that the common clinical practice of rotating the anatomic regions used for insulin injections increases day-to-day variation in blood glucose concentration. Use of a single anatomic region, eg, the abdomen, for all insulin injections may reduce this variation and allow greater precision in the adjustment of insulin doses.

Abdomen↗