Autocrine Mechanisms Modulating Endocrine Regulation of Mammary Gland Function

Bennett, Crispin N (1993) Autocrine Mechanisms Modulating Endocrine Regulation of Mammary Gland Function. PhD thesis, University of Glasgow.

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This thesis examines the mechanisms by which local changes in the frequency and efficiency of milk removal modify the regulation of the mammary gland by circulating galactopoietic hormones. Individual mammary glands of a suckled, lactating rabbit were seeded to allow effects arising from engorgement of the gland with milk to be studied. Accumulation of milk in the mammary gland significantly reduced mammary prolactin receptor number, which was assessed in 4.5 M-MgCl2 stripped microsomal membremes. This reduction in receptor number was apparent at the end of the normal (24 h) suckling interval and preceded the locally-induced decrease in the rate of milk accumulation previously shown to occur after this time. The effect of milk accumulation on hormone binding was due, at least in part, to the actions of the feedback inhibitor of lactation (FIL). This milk constituent, which is thought to be responsible for the local control of milk secretion, reduced both prolactin and IGF-I receptor number when introduced into the mammary gland via the teat duct. In contrast, in the goat, more frequent removal of milk for 9 days did not affect prolactin receptor number, although it did stimulate the rate of milk secretion. In this case, it was possible that there was an effect on the distribution of receptors within the secretory cell. The final part of this study investigated the mechanism of FIL action on hormone receptor number. For this purpose, methods were developed for the isolation and culture of mammary cells, by enzymic digestion of mid-lactation mouse mammary gland. Incubation of isolated cells with a 10-30 kDa goat whey fraction containing FIL, for 2 hours, resulted in prolactin receptors being relocated from cell- surface to intracellular sites, without affecting total receptor number. This FIL-induced reduction in hormonal sensitivity did not appear to mediate FIL's acute effects on protein secretion, since these were independent of exogenous prolactin during this short-term culture. In conclusion, this study demonstrates local modulation of endocrine regulation of the lactating mammary gland. The effects of milk accumulation and alterations in milking frequency and efficiency on mammary prolactin receptor number and distribution are due, at least in part, to FIL. These FIL-induced changes in cellular sensitivity to circulating galactopoietic hormones could have important long-term effects on milk yield and mammary differentiation.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Additional Information: Adviser: Chris Knight
Keywords: Endocrinology, Physiology
Date of Award: 1993
Depositing User: Enlighten Team
Unique ID: glathesis:1993-74781
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 27 Sep 2019 16:31
Last Modified: 27 Sep 2019 16:31

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