Livestock Production Science 66 2000 169–176 www.elsevier.com locate livprodsci
The importance of cell division in udder development and lactation
C.H. Knight
Hannah Research Institute , Ayr KA6 5HL, UK
Abstract
The mammary secretory cell population increases in an exponential fashion during pregnancy in all species studied, as a consequence of very high rates of cell division. After parturition the mitotic index drops dramatically, but a limited amount
of proliferation does continue, at least until the time of maximum milk yield. This is particularly true of rodents but also occurs in dairy species. During declining lactation apoptosis exceeds cell division, so the size of the cell population falls and
it is this decrease which is responsible for the reduction in milk yield. Many factors influence cell division. In addition to well known hormones such as ovarian steroids, prolactin and growth hormone, and growth factors such as epidermal growth
factor and insulin-like growth factor-1, there are also effects of milking frequency and nutrition. Some of these same factors are now also known to regulate apoptosis. The challenge for the future is to understand more about the relationships between
apoptosis and cell division in the mammary gland; for instance, are the two mutually exclusive and independent or is apoptosis important in preparing the gland for renewed cell division? To this end, we have developed a lactation rescue
model which will allow us to study interactions between apoptosis and cell division in lactating mouse and cow mammary glands.
2000 Elsevier Science B.V. All rights reserved.
Keywords : Mammary gland; Development; Cell proliferation; Apoptosis; Lactation
1. Introduction have depressed milk yield, and research has shown
this to be a consequence of low blood concentrations Growth of the mammary gland is termed mam-
of growth hormone GH and insulin-like growth mogenesis. There are two distinct phases, growth
factor-1 IGF-1 reducing peripubertal mammary cell prior to first conception and then cyclical waves of
proliferation Weber et al., 1999. The GH IGF axis proliferation, secretion and involution during recur-
is not the only endocrine regulator of mammary ring lactation cycles. The most important part of the
proliferation, but it is an important element. During first phase is the allometric growth which occurs just
the life of the cow the mammary cell population before and around puberty, since inappropriate de-
probably expands by more than 100-fold although velopment at this stage can have long term repercus-
precise quantification is difficult with the vast sions Sejrsen, 1994. Rapidly-reared heifers often
majority of this proliferation taking place during pregnancy under the stimulatory influence of ovarian
steroids and peptide mammogens, including GH.
Tel.: 1 44-1292-674-046; fax: 1 44-1292-674-047. E-mail address
: knightchri.sari.ac.uk C.H. Knight.
Treatment of late pregnant goats with exogenous GH
0301-6226 00 – see front matter
2000 Elsevier Science B.V. All rights reserved. P I I : S 0 3 0 1 - 6 2 2 6 0 0 0 0 2 2 4 - 4
170 C
.H. Knight Livestock Production Science 66 2000 169 –176
increases cell proliferation and subsequent milk yield much milk as the LGM cows, from 1.3-times as
Knight et al., 1994, and there is much evidence to much udder tissue Sorensen et al., 1998. Clearly,
show that the number of secretory cells present in the the amount of secretory tissue is an important
mature udder is a primary determinant of milk yield determinant of milk yield, and selection for output
Sorensen et al., 1998. Using bromodeoxyuridine has indeed resulted in larger udders.
injections to ‘‘tag’’ proliferating cells and then Udder volume is a crude measurement of total
counting these cells in histological sections obtained tissue mass, and provides no information on the
by biopsy, we have observed labelling indices of relative proportions of secretory and non-secretory
around 10 in late pregnancy, subsequently falling tissue. Different tissue types can be distinguished by
precipitously after parturition; mammary cells do not imaging techniques such as X-ray, computed tomog-
proliferate extensively during lactation, although raphy CT scanning and magnetic resonance imag-
they retain the potential to divide and simple treat- ing MRI. We have used MRI in vivo in goats
ments such as frequent milking are mitogenic Wilde Fowler et al., 1990 and others have used CT
et al., 1987. GH administered in early lactation does scanning in excised udders of heifers Sorensen et
not stimulate proliferation Knight et al., 1994, but al., 1987, but there is no possibility of using either
later in lactation its mitogenic capacity returns method for dairy cows in vivo because cows are
Capuco and Byatt, 1998. Whether other mitogens simply too big. The alternative approach is to
are only active at certain stages of the lactation cycle measure the composition of the tissue by biochemi-
is not known, but it is apparent that observations cal or histological analysis. We now do this in needle
made at one point in time cannot be extrapolated to biopsy samples using a mechanical biopsy tool
cover all circumstances. Magnum; C.R. Bard, Covington, GA, USA which
allows for repeated measurements with relatively little disturbance to the cow. If it is the number of
2. Importance of cell number: comparative secretory cells which ultimately determines yield,
