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Biomedical subjects

M Peaker

Publications and source records attributed to M Peaker.

At least 19 recordsLinked to original sources
PubMed2000

Transport of milk constituents by the mammary gland.

This review deals with the cellular mechanisms that transport milk constituents or the precursors of milk constituents into, out of, and across the mammary secretory cell. The various milk constituents are secreted by different intracellular routes, and these are outlined, including the paracellular pathway between interstitial fluid and milk that is present in some physiological states and in some species throughout lactation. Also considered are the in vivo and in vitro methods used to study mammary transport and secretory mechanisms. The main part of the review addresses the mechanisms responsible for uptake across the basolateral cell membrane and, in some cases, for transport into the Golgi apparatus and for movement across the apical membrane of sodium, potassium, chloride, water, phosphate, calcium, citrate, iodide, choline, carnitine, glucose, amino acids and peptides, and fatty acids. Recent work on the control of these processes, by volume-sensitive mechanisms for example, is emphasized. The review points out where future work is needed to gain an overall view of milk secretion, for example, in marsupials where milk composition changes markedly during development of the young, and particularly on the intracellular coordination of the transport processes that result in the production of milk of relatively constant composition at a particular stage of lactation in both placental and marsupial mammals.

Amino Acids↗
PubMed1998

Local control of mammary development and function.

For the mother, lactation represents the final stage of an investment in her genetic material. Like any investment it is costly and, hence, it needs to be carefully controlled. To her offspring, lactation means survival, so it must happen at any cost. This apparent conflict is rationalized by the mother devolving some control to the offspring while retaining ultimate sanction herself. Part of this results from overt and more subtle influences of the presence of young on the mother's endocrine system, but an equally important part operates at each mammary gland to ensure that output is appropriate to the needs of the young, and no more. The young exert influence by removing milk, while the mother retains control by responding on an hour to hour basis to the presence of milk in the gland. Local control is inevitably most evident where secretion itself is concerned, but also operates to influence lactogenesis, gland development and, eventually, gland involution. This paper will review local control of mammary function, emphasising the important role played by an autocrine inhibitory protein, the feedback inhibitor of lactation.

Animals↗
PubMed1998

Local control of the mammary gland.

Studies on increasing the frequency of milking in dairy animals have led to the uncovering of the mechanism by which tactical control of the rate of milk secretion is achieved locally within each mammary gland, against a strategic, systemic control by the hormones that maintain all glands in the secretory condition. Experiments in vivo established that the response is local, and were compatible with the hypothesis that milk contains an inhibitor of its own secretion which accumulates during storage within the lumen of the mammary gland and which acts in an autocrine manner on the secretory cells. Isolation of a protein, initially from goats' milk, called FIL (feedback inhibitor of lactation) has enabled, and is enabling, further studies to be done from the whole-animal down to the molecular level. Examples at the whole-animal level are: the effects of immunization against FIL on the rate of secretion; the concentration of FIL and the kinetics of its formation and breakdown; the importance of the internal structure of the mammary gland and the capacities of the alveolar and ductular storage regions in determining feedback inhibition; differences between individuals and species influencing the degree of control exerted by FIL in matching supply of milk to demand by the young. Other local control mechanisms at the onset and cessation of lactation, including mammary distension, are also discussed.

Animals↗
PubMed1998

Autocrine regulation of milk secretion.

Mammary development and the rate of milk secretion are regulated by frequency and completeness of milk removal. This regulation occurs through chemical feedback inhibition by a milk constituent. Novel, immunologically related milk proteins able to perform this function have been isolated from caprine, bovine and human milk, based on their ability to inhibit milk constituent synthesis in mammary tissue and cell cultures, and to decrease temporarily milk secretion when added to milk stored in the mammary gland. Inhibition is concentration-dependent, suggesting that milk accumulation and removal is accompanied by cyclical changes in inhibitor accretion and depletion in milk. Feedback inhibition is an autocrine mechanism: the caprine inhibitor, termed FIL (feedback inhibitor of lactation) is synthesized by mammary epithelial cells in primary culture. Inhibition is by reversible blockade of the secretory pathway, an effect which, by down-regulating cell-surface hormone receptors, has longer-term consequences on epithelial cell differentiation. Treatment of goat mammary epithelial cell cultures with caprine FIL initially decreased milk protein secretion and subsequently reduced milk protein messenger RNA abundance. Thus the actions of a single milk constituent can bring about both the effect of milking frequency on milk secretion rate and a sequential modulation of cellular differentiation which acts to sustain the secretory response. Long-term regulation, through changes in galactopoietic hormone receptors, also provides an efficient mechanism for integrating acute intramammary regulation of lactation with strategic endocrine control of mammary tissue development.

Animals↗
PubMed1996

Effects of immunization against an autocrine inhibitor of milk secretion in lactating goats.

1. Lactating goats were immunized against the goat's milk protein identified as a feedback inhibitor of lactation (FIL). Immunization was by three treatments during the declining stage of lactation. 2. When antibodies to FIL were consistently detected in milk (in response to the third treatment), the rate of decline in milk secretion was significantly reduced compared with sham-immunized controls. Such a response was not apparent with the first two treatments when serum but not milk titres of anti-FIL were raised. 3. When one gland of immunized goats was switched (after the third immunization) from twice- to once-daily milking, the ipsilateral decrease in the rate of milk secretion was reduced significantly compared with sham-immunized goats. 4. The results are compatible with the hypothesis that the autocrine agent FIL acts during milk accumulation as an inhibitor of milk secretion.

Animals↗
PubMed1996

Feedback control of milk secretion from milk.

Extracellular storage allows biologically-active substances in milk to influence mammary function. Among these factors is one which regulates the rate of milk secretion acutely according to frequency or completeness of milk removal in each mammary gland. The active factor in goat's milk has been identified by screening milk constituents for their ability to inhibit milk constituent secretion in tissue and cell culture bioassays, and found to be a novel milk protein. The proteins identified by bioassy in vitro, also inhibited milk secretion in lactating goats in a reversible, concentration-dependent manner. This protein, termed FIL (feedback inhibitor of lactation), acts by reversible blockade of constitutive secretion in the mammary epithelial cell. As the inhibitor is synthesized in the same epithelial cells, feedback inhibition is, therefore, an autocrine mechanism. FIL's unusual mechanism of action also influences other aspects of mammary function. Acute disruption of mammary membrane trafficking is associated with downregulation of prolactin receptors and followed by a decrease in epithelial cell differentiation. Thus, in addition to acutely-regulating milk secretion, FIL may induce the adaptation in mammary cell differentiation which acts in vivo to sustain the secretory response to a sustained change in milk removal. In the long term, matching of milk output to demand is achieved by a change in mammary cell number. This developmental response is also local in nature. Whether it too is due to autocrine modulation by FIL of mechanisms influencing cell proliferation or survival, or elicited by another milk-borne factor, remains to be determined.

Animals↗
PubMed1996

Sex ratio and litter size in the guinea-pig.

A significant relationship between sex ratio and litter size at birth was observed in the young of guinea-pigs caged singly from 8 weeks of age and during their first pregnancy; a male was present only at or around oestrus. Small litters (1-2 young) had significantly more males than did large litters (4-5 young). Such a relationship was not apparent in animals housed communally, whether young or older or in their second pregnancy. Litters in late pregnancy (day 63) or at delivery were significantly smaller than at mid-pregnancy (day 35). A significant negative relationship was found between litter size and bodymass at birth and to at least 63 days of age. Growth rates during the period of lactation were lower in animals born in large litters. The possible adaptive significance of a plastic relationship between litter size and sex ratio is considered together with the physiological mechanism that might be involved.

Animals↗
PubMed1995

Autocrine regulation of milk secretion by a protein in milk.

Frequency or completeness of milk removal from the lactating mammary gland regulates the rate of milk secretion by a mechanism which is local, chemical and inhibitory in nature. Screening of goat's milk proteins in rabbit mammary explant cultures identified a single whey protein of M(r) 7600 able to inhibit synthesis of milk constituents. The active whey protein, which we term FIL (Feedback inhibitor of Lactation), also decreased milk secretion temporarily when introduced into a mammary gland of lactating goats. FIL was synthesized by primary cultures of goat mammary epithelial cells, and was secreted vectorially together with other milk proteins. N-terminal amino acid sequencing indicated that it is a hitherto unknown protein. The evidence indicates that local regulation of milk secretion by milk removal is through autocrine feedback inhibition by this milk protein.

Amino Acid Sequence↗
PubMed1995

The effects of relaxin on the response of intramammary pressure and mammary blood flow to exogenous oxytocin in the goat.

Lactating goats were given relaxin (50 micrograms) by close-arterial infusion into one mammary gland. The increase in intramammary pressure and in mammary blood flow elicited by exogenous oxytocin i.v. was attenuated by relaxin in goats during pregnancy and early lactation but not in a group studied during the oestrous cycle. Intramammary pressure in both mammary glands was affected at the dose of relaxin used. It is concluded that a change in responsiveness of the mammary myoepithelium to oxytocin is one possible effect of relaxin, acting directly or indirectly, circulating systemically during pregnancy and produced locally by the mammary gland at the onset of and during lactation.

Animals↗
PubMed1994

Inhibitory effect of milk fat on milk secretion in the mouse: a re-examination.

Lactating mice were treated I.P. with cow milk, skim milk, milk lipid extract, preparations of milk fat globule membranes and fat globule-enriched milk (cream). Milk, but not skim milk, inhibited litter growth significantly. None of the fractions of milk fat globules had any apparent effect on litter growth. Litter growth was reduced markedly and maternal health adversely affected by cream. It is concluded that previous studies in which milk was injected I.P. cannot be taken to indicate that milk contains a lipid or lipid-soluble inhibitor of milk secretion in addition to the protein inhibitor discovered in milk more recently.

Animals↗
PubMed1992

Production of parathyroid hormone-related protein by the mammary gland of the goat.

Parathyroid hormone-related protein (PTHRP) has been quantified by sensitive specific immunoassays in mammary venous blood and milk from 7 days before to 7 days after parturition in the goat. A significant venous-arterial concentration gradient in plasma PTHRP 1-86 concentrations was demonstrated across the mammary gland, indicating that PTHRP enters the maternal circulation and may have a role in calcium homoeostasis during lactation. Significant and sustained increases in mammary venous and milk PTHRP 1-86 concentrations were found from 1 day before parturition to 7 days afterwards, with peak concentrations of 1.57 +/- 0.58 pmol/l (plasma) and 8.69 +/- 2.95 nmol/l (milk) (mean +/- S.E.M.) occurring on day -1 and the day of parturition respectively. Estimates of the mammary output of PTHRP into plasma in four goats averaged 9% (range 1-25%) of that secreted into milk. Suppression of maternal prolactin concentrations by bromocriptine significantly reduced milk yield and the mammary venous PTHRP concentration, without affecting the concentration of PTHRP in milk. In conclusion, parturition in the goat is associated with a sustained increase in secretion of PTHRP into both plasma and milk; the former may be involved in maternal calcium homoeostasis, whereas the latter may have a role in the neonate.

Animals↗
PubMed1991

Mammary gland blood flow and plasma concentrations of 6-keto-prostaglandin F1 alpha in the goat.

1. Mammary blood flow and concentrations of the stable metabolite of prostacyclin, 6-keto-prostaglandin F1 alpha, in mixed venous and mammary venous blood plasma have been measured in five lactating goats at various times during the day. 2. Natural variation in blood flow was not associated with any local release of 6-keto-prostaglandin F1 alpha into the mammary venous circulation.

6-Ketoprostaglandin F1 alpha↗