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Biomedical subjects

I A Forsyth

Publications and source records attributed to I A Forsyth.

At least 37 records · Page 2Linked to original sources
PubMed1991

The mammary gland.

In vivo studies have shown that the growth of the mammary gland is regulated by a complex synergistic interaction of protein, steroid and thyroid hormones, but it has proved difficult to fully reproduce these effects in vitro. It is becoming apparent that the hormones classically recognized as involved in mammary growth (oestrogen, progesterone, prolactin, GH, adrenal corticoids, triiodothyronine) bring about effects on epithelial cell proliferation at least in part through growth factors produced at distant sites (such as the liver) and also locally by mammary tissue, both parenchyma and stroma. Growth factor receptors can be demonstrated in mammary tissue. Receptor occupancy generates intracellular signals which enable cells to progress through the cell cycle, leading in ways still not understood to DNA synthesis and cell division. Within the mammary gland there probably exists a balance of stimulatory factors (such as IGFs and EGF/TGF-alpha) and inhibitory factors (such as TGF-beta). Interactions between epithelial and stromal cells, involving growth factors and the extracellular matrix, bring about pattern formation. Growth factors may also play some part in mammary differentiation and function, although the evidence here is less clear. Growth factors are also implemented in the failure of growth regulation which neoplastic transformation represents. Breast cancer cells can synthesize and secrete a variety of growth factors which may stimulate tumour growth through local autocrine/paracrine mechanisms. The oestrogen dependence of some breast cancers may involve oestrogen regulation of and interaction with growth factors, progression to hormone independence involving loss of this control. It is significant that the proteins which protooncogenes encode include growth factors and growth factor receptors. Much remains to be learnt about the nature and control of growth factors produced by and acting on the mammary gland. In breast cancer, this research offers the possibility of new methods of diagnosis and treatment.

Animals↗
PubMed1990

Sensitivity of goats to a light pulse during the night as assessed by suppression of melatonin concentrations in the plasma.

This study investigates the ability of a 1 h light pulse of different intensities at night to suppress plasma melatonin in goats. Six female Saanen dairy goats, about 2 yr old, were housed in a light-tight shed. The goats were habituated for 1 wk to an 8L:16D photoperiod (40.70 +/- 4.16 microW/cm2; 137 +/- 14 lux), lights on 0800 h. A 1 h light pulse, of different intensity on each occasion, was given from 1900 to 2000 h. Light intensity was measured by using a lux meter (mean of 36 measurements at goat's eye level). Five different light intensities were given during December in the order 4.22 +/- 0.62 microW/cm2 (14.2 +/- 2.1 lux), 0.68 +/- 0.09 microW/cm2 (2.3 +/- 0.3 lux), 0.26 +/- 0.004 microW/cm2 (0.87 +/- 0.14 lux), darkness, 40.70 +/- 4.16 microW/cm2 (137 +/- 14 lux), with 1-3 d between treatments. The goats were bled hourly from 1500 to 1900 h and every 15 min from 1900 to 2100 h, and a last bleed occurred at 2200 h. Dark-phase samples were taken in dim red light (less than 0.03 microW/cm2; 0.1 lux). Plasma was assayed for melatonin by radioimmunoassay. Suppression of melatonin concentrations increased as light intensity increased as follows: Darkness, 0%; 0.26 +/- 0.004 microW/cm2; 0%; 0.68 +/- 0.09 microW/cm2; 43.1%; 4.22 +/- 0.62 microW/cm2, 71.1%; 40.70 +/- 4.16 microW/cm2, 81.2%. Suppression was significant (P less than 0.05) at light intensities greater than 0.68 microW/cm2, 2.3 lux. A hyperbolic relationship existed between percent suppression and light intensities.

Analysis of Variance↗
PubMed1989

Mammary development.

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Animal Nutritional Physiological Phenomena↗
PubMed1989

Cloning and expression of ovine placental lactogen.

Ovine placental lactogen (oPL) is active in a wide range of GH and PRL assays, a property that it shares with human GH (hGH). In addition, oPL is one of a small number of hormones that bind the human GH receptor with high affinity. In order to compare the sequence of oPL to the sequences of other members of the GH family, full-length cDNA clones have been isolated. These clones predict that the full sequence of oPL contains 198 amino acids preceded by a 38 amino acid signal sequence. The mature oPL sequence includes six cysteine and two tryptophan residues and shows substantially more identity to bovine PL (67%) and oPL (49%) than to mouse (31%) or human (25%) PL or to oGH (28%) or (26%) hGH. Like the natural hormone, oPL expressed in mammalian tissue cells binds with high affinity to a soluble form of the recombinant hGH receptor. Thus, oPL binds to the human receptor in spite of having a sequence that is considerably divergent from hGH. Interestingly, the sequence of oPL differs from hGH at most of the amino acids recently found by mutagenesis studies to be important residues in the binding of hGH to the human receptor.

Amino Acid Sequence↗
PubMed1989

Stimulation of DNA synthesis in cultures of ovine mammary epithelial cells by insulin and insulin-like growth factors.

Ovine mammary epithelial cell clumps (30-90 microns) were plated onto attached gels of rat tail collagen in serum-free medium. Synthesis of DNA by these cultures could be stimulated by insulin-like growth factor-I (IGF-I) with a median effective dose of 5 micrograms/l, irrespective of stage of pregnancy. The time-course of response, however, was significantly slower in cells prepared from mammary tissue of non-pregnant and early pregnant sheep compared with sheep later in pregnancy. IGF-II had approximately 10% of the potency of IGF-I in stimulating DNA synthesis. Insulin acted over a wide concentration range and produced a maximum rate of stimulation not significantly different from that produced by IGF-I. These results are consistent with actions through the type-I IGF receptor although insulin may also act through its own receptor, possibly stimulating local IGF-I production. It is concluded that IGF-I is an important mitogen for ovine mammary epithelial cells.

Animals↗
PubMed1987

Relationships between plasma hormone concentrations, udder development and the production of early mammary secretions in twin-bearing ewes on different planes of nutrition.

Ewes carrying twin fetuses were maintained during late pregnancy on a uniformly high plane (well fed), a uniformly low plane (underfed) or a low plane rising to a high plane (refed) of nutrition. The maternal plasma concentrations of hormones concerned with udder development, colostrum production and milk secretion were measured in samples obtained during the last 32 d before and the first 18 h after birth. Udder weights were derived from their linear dimensions, the yields of mammary secretions by hand milking during the first 18 h after birth and the transition from colostrum to milk was indicated by changes in the concentrations of lactose, lipid and immunoglobulin G. Underfeeding reduced prenatal udder development and colostrum accumulation and delayed the post-natal transition to milk secretion. Refeeding previously underfed ewes to a high plane during the last 5 d before birth had no effect on udder growth, but it did return the secretory functions of udder tissue to the levels observed in well-fed ewes. Nutritional effects on the plasma concentrations of insulin, placental lactogen, prolactin, cortisol and oestradiol-17 beta were small or absent. The relative changes in the plasma concentrations of growth hormone and insulin were such that the growth hormone: insulin ratio increased markedly during the last 11 d before birth in the underfed and refed ewes but not in the well-fed ewes. These differences in the growth hormone: insulin ratio were associated with greater increases in udder growth rate in the underfed and refed ewes than in the well-fed ewes. The plasma concentrations of progesterone decreased before birth in all ewes, but the decrease was delayed by underfeeding and refeeding rapidly overcame this effect. The slower progesterone withdrawal in the underfed ewes was associated with a delay in lactogenesis. It is concluded that the nutritionally induced changes in the growth hormone: insulin ratio and in the progesterone concentrations were the most likely endocrine determinants of the observed differences in the rates of mammogenesis and lactogenesis, respectively, but possible independent effects of substrate supply to the udder remain to be clarified.

Animals↗
PubMed1987

Effects of continuous intravenous infusion of an ovine placental extract enriched in placental lactogen on plasma hormones, metabolites and metabolite biokinetics in non-pregnant sheep.

Continuous intravenous infusions of saline or of a placental extract containing ovine placental lactogen were given to three non-pregnant, non-lactating ewes over periods of 36 h, 1 week apart. During saline infusion no placental lactogen was detected in jugular vein plasma. but infusion of the placental extract raised the placental lactogen concentration from undetectable to 40-50 micrograms/l, similar to concentrations in ewes with one fetus on day 90 of pregnancy. By comparison with the saline control period, infusion of the placental extract consistently increased both plasma concentrations and irreversible loss of nonesterified fatty acids. Plasma concentrations of glucose and urea, but not irreversible loss of these metabolites, were consistently increased. Although the placental extract was not subjected to extensive purification, it was enriched in placental lactogen and contained no detectable contamination with insulin, prolactin or growth hormone. The results are suggestive of a role for placental lactogen in modifying metabolism and acting during pregnancy to provide nutrients for fetal metabolism.

Animals↗
PubMed1986

Variation among species in the endocrine control of mammary growth and function: the roles of prolactin, growth hormone, and placental lactogen.

Prolactin, growth hormone, and placental lactogen form a family of structurally related hormones, which may have evolved from a common ancestral peptide. Prolactin and growth hormone are present in all mammals, but the biological activity associated with placental lactogen has been detected in only some groups. Attempts to detect placental lactogen using bioassay and radioreceptor assay are reported and have been unsuccessful in an insectivore (the shrew), a bat, an edentate (the armadillo), a lagomorph (the rabbit), several carnivores (dog, cat, ferret), perissodactyls (horse, zebra, rhino), and, within the artiodactyls, pigs. Placental lactogenic activity has been detected in primates (chimpanzee, orangutan), rodents (voles, Pinon mouse, guinea-pig, mara), and in numerous artiodactyls (llama, giraffe, several species of deer, antelope, gnu, gazelle, musk ox, cape buffalo, Barbary sheep, several sheep of the genus Ovis, goat, and cow). These results confirm and extend the work of others and are discussed in relation to the evolution of these hormones. In synergism with steroid and thyroid hormones, protein hormones of the prolactin and growth hormone family play a crucial role in stimulating the development of the mammary gland, the differentiation and function of mammary cells to secrete milk, and in the systemic adjustments in maternal metabolism in pregnancy and lactation. Studies in vitro have shown that mammary tissues from several species synthesize milk components in response to insulin plus adrenal corticoid plus prolactin. However, there are also species differences in minimal hormonal requirements for lactogenesis. In vivo, for example, rabbits will initiate or sustain lactation in response to prolactin alone, whereas sheep and goats require prolactin plus growth hormone plus adrenal corticoid plus thyroid hormone. Measurement of hormone concentrations in the plasma of pregnant animals shows considerable differences among species in the pattern of secretion of lactogenic hormones to bring about mammary development. A surge of prolactin secretion occurs at parturition but may not be essential in the initiation of lactation. The timing of progesterone withdrawal correlates well with lactogenesis in eutherian mammals, but species differ in the mechanisms at parturition which bring this about. Marsupials show a quite different pattern of suckling-induced lactation. In maintaining lactation the greatest contrast is between ruminants, in which growth hormone is of particular importance, and other mammals, in which reduction of prolactin secretion with bromocriptine rapidly suppresses milk synthesis and secretion.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

Hormone concentrations, mammary development and milk yield in goats given long-term bromocriptine treatment in pregnancy.

Ten British Saanen goats were treated daily with 5 mg bromocriptine intramuscularly from week 8 of pregnancy until week 20 (day 140). By comparison with untreated control goats (n = 8), concentrations of prolactin in plasma were suppressed throughout the treatment period and remained significantly lower until 3 days prepartum, parturition occurring on day 153 +/- 0.7 (mean +/- S.E.M., n = 10). Growth hormone concentrations were low, but the incidence of levels exceeding 1 microgram/l was increased in bromocriptine-treated goats. Plasma concentrations of placental lactogen, progesterone and oestrone sulphate were unaffected. The accumulation of pre-colostrum in the udder (lactogenesis stage I) was not affected by bromocriptine treatment in goats carrying twin fetuses, but in goats with single kids it was delayed by about 4-6 weeks to week 17 of pregnancy. Secretion could not be expressed from the udder and the concentration of alpha-lactalbumin in plasma remained low. Udder volume was significantly reduced in week 15-16 but not week 20-21 of pregnancy by bromocriptine treatment. Milk yields after 50 or 203 days of lactation were not significantly different from those in control goats. Placental lactogen concentrations in late pregnancy and udder volume in week 20-21 were the only variables measured which correlated with milk yield post partum. It is concluded that in vivo placental lactogen is an effective mammotrophic hormone, although less potent than prolactin as evidenced by the delay in lactogenesis stage I in bromocriptine-treated goats bearing single kids.

Animals↗
PubMed1984

Dopamine reduces the receptor binding activity and not the secretion rate of placental lactogen in vitro.

Incubation with high concentrations of dopamine (greater than or equal to 10(-3) mol/l) depressed the ability of goat placental lactogen, human placental lactogen, ovine prolactin and human growth hormone to compete with labelled hormone in radioreceptor assays for lactogenic activity, with the greatest effects on placental lactogen. The activity of ovine prolactin in a radioimmunoassay was also depressed. The effects on human placental lactogen depended on the concentration of dopamine and on the time and temperature of incubation. Therefore, effects on activity, rather than on secretion rate, appear to explain the inhibition by dopamine of placental lactogen in the medium of placental explant cultures.

Animals↗
PubMed1984

Fatty acid synthesis by explant cultures from the mammary glands of goats on days 60 and 120 of pregnancy.

Explants of mammary glands from 60-day pregnant goats showed a mean fourfold increase in fatty acid synthesis from acetate when cultured with insulin+ cortisol. Epithelial cells increased their area by 60% but no secretory activity was induced. In 120-day pregnant goats, fatty acid synthesis and epithelial cell area were greater than at day 60 of pregnancy and were unaffected by hypophysectomy or by daily treatment with bromocriptine from day 60. Neither increased further on culture of mammary explants in insulin + cortisol. Ovine prolactin increased fatty acid synthesis two-fold when added to insulin + cortisol in cultures of mammary tissue from goats on day 60 of pregnancy and secretory activity was induced. On day 120 of pregnancy insulin + cortisol + prolactin sustained or slightly stimulated both fatty acid synthesis and the extensive secretion present in the tissue at the start of culture. Synthesis of medium-chain fatty acids of milk-fat was also sustained by prolactin in one goat. An atmosphere of air was found to maintain normal histological structure of the mammary gland. By contrast, in 95% oxygen, explants from goats which were 60 days pregnant showed epithelial cells filling the lumina of ducts and alveoli in 60% of explants and a poor response to prolactin.

Acetates↗
PubMed1983

Simultaneous determinations of uterine blood flow and plasma concentrations of placental lactogen in late-pregnant goats.

Blood flow in the middle uterine artery was measured with electromagnetic blood flow probes, and placental lactogen in jugular and uterine venous plasma was estimated as total lactogenic activity using a radioreceptor assay. There was no circadian variation in uterine arterial blood flow in late pregnancy (Days 105-124) and the pattern of blood flow varied between goats. Blood flow was quite stable for periods of up to 40 min although at other times a rapid fall (by up to 90%) was followed by a gradual recovery. These spontaneous changes lasting up to 30 min could not be consistently related to postural or behavioural changes. Acute decreases of about the same duration could also be induced by administration of adrenaline. In the short-term there was no association between uterine blood flow and total lactogenic activity in the peripheral circulation during spontaneous or adrenaline-induced depression of blood flow. More limited short-term observations on total lactogenic activity in the uterine vein also failed to show a relationship with blood flow in the uterine artery.

Animals↗
PubMed1983

Milk-fat synthesis by lobules prepared from rabbit mammary gland: response to insulin, corticosterone, prolactin and progesterone.

Multi-alveolar mammary structures (mammary lobules) were prepared from mammary glands of pseudopregnant rabbits by controlled digestion with collagenase and hyaluronidase. The overall rate of fatty acid synthesis and the proportion of milk-specific fatty acids (C8:0 and C10:0) synthesized by these lobules when cultured with insulin, corticosterone and prolactin were measured. Maximum response to physiological concentrations of prolactin (1.1 or 2.2 nmol/l) occurred in the presence of insulin (1.7 mumol/l) and corticosterone (0.58 mumol/l). In general, the results obtained on the effect of progesterone were negative. Though explants showed a ninefold greater response to prolactin per mg DNA than did mammary lobules, the latter have the advantage of being easily prepared for culture in large numbers. Reduction to below 500 microns diameter and culture in conditions which allow cell outgrowth onto plastic limited their response to prolactin. The probable roles of membrane damage by digesting enzymes and of tissue architecture in limiting prolactin response are discussed.

Animals↗
PubMed1983

Study of prolactin levels in the ferret.

A radioimmunoassay for canine prolactin has been used to measure prolactin in the ferret. Serial dilutions of extracts of ferret pituitary glands and of ferret plasma yielded curves that were parallel with the canine prolactin standard curve. The sensitivity, accuracy, reproducibility and precision of the assay were within acceptable limits. Plasma prolactin levels increased after the administration of thyrotrophin releasing hormone (TRH) or chlorpromazine, but not after giving luteinizing hormone releasing hormone. Female ferrets, which were anoestrous, oestrous or spayed, and male ferrets had similar basal prolactin levels when sampled under sodium pentobarbitone anaesthesia. These basal levels were higher than in conscious males and the latter also showed a lesser response to TRH. Hypophysectomy significantly reduced basal prolactin levels in female ferrets by 2 h postoperatively and abolished the response to TRH.

Animals↗
PubMed1982

Culture of bovine mammary epithelial cells on collagen gels.

A method for the isolation of lobules of acini from bovine mammary gland and their storage in liquid nitrogen is described. After further dissociation of freshly prepared or frozen lobules, clumps of cells are obtained which attach to collagen gels and give rise to colonies which, on morphological criteria, appear predominantly epithelial. Storage for up to 6 months did not adversely affect viability. Increase in colony area involved cell division, was more rapid in air than in 95% oxygen and was enhanced by fetal calf serum.

Animals↗
PubMed1981

Novel multialveolar epithelial structures from rabbit mammary gland that synthesize milk specific fatty acids in response to prolactin.

Multialveolar mammary epithelial structures have been prepared from rabbit mammary gland by treating the tissue with collagenase plus hyaluronidase. These structures synthesize milk specific fatty acids when cultured with physiological concentrations (0.5 micrograms/ml) of prolactin in the presence of insulin and corticosterone. They have many of the advantages but few of the disadvantages of either mammary explants or primary cells in culture. For example, they are easily prepared in large numbers and respond to prolactin in culture even in the absence of serum or other tissue extracts. Because their level of organization is intermediate between that of explants and single cells, they provide a complementary system for studies on mammary differentiation.

Animals↗