Milk proteins, prolactin

Among its effects on the epithelial cells of the mammary alveoli prolactin stimulates the production of the major milk proteins casein and lactalbumin [64,66-69,74-76]. Mouse mammary explants incubated in vitro with insulin and a corticosteroid produce very little of these proteins, but addition of prolactin to the culture medium induces their synthesis 10-20-fold within about 24 h. As has already been discussed, there is some uncertainty about the importance of glucocor-... 

In addition to its effects on synthesis of milk proteins themselves, prolactin also induces the production in the mammary gland of other proteins/enzymes involved in production of milk components. Lactose synthetase and enzymes of lipid metabolism, including acetyl-CoA carboxylase and lipoprotein lipase, are among these inducible enzymes [75]. 

A role for cyclic AMP as a mediator for the actions of prolactin has been proposed, but the bulk of the evidence available suggests that it is not directly involved. It is possible that levels of cyclic AMP-dependent protein kinase are limiting, rather than cyclic AMP itself, and that these can be increased by prolactin, presumably by induction of the appropriate genes [67]. Cyclic AMP derivatives do not mimic the actions of prolactin in in vitro systems. Indeed, they may inhibit some actions of the hormone, including stimulation of synthesis of milk proteins, fatty acids, DNA and RNA in mammary gland explants [79-81]. 

It will be clear from what has been presented in this chapter that the mechanism of action of prolactin remains far from clear. Much progress has been made in the past few years, particularly in the characterization of receptors for prolactin and in understanding the induction of expression of the genes for milk proteins that are controlled by prolactin. The signal transduction events which link these two processes remain unclear, however. A few of the main aspects of prolactin activity that need explanation at the biochemical level will be summarized here. 

Prolactin, produced in response to suckling of an infant, stimulates the synthesis of milk proteins during lactation. 

D. Prolactin causes synthesis of the milk protein a-lactalbumin, which stimulates lactose synthesis. 

Translational and transcriptional control are sometimes combined. For example, insulin (which regulates the synthesis of a large number of substances) and prolactin (another hormone) are required together for production of casein (milk protein) in mammary tissue. Both hormones are needed to initiate transcription but prolactin in addition, increases the lifetime of casein mRNA. 

Different eukaryotic mRNAs may have widely differing half-lives and the more stable the mRNA, the more protein that can be translated from it. Various factors may affect the stability of specific mRN. For example, in the presence of the peptide hormone prolactin, casein mRNAs are specifically stabiliwd during lactation, thereby increasing the level of expression of these milk proteins. 

Lactoferrin is the major whey protein present in breast milk (Teraguchi et ah, 1996) with many microbicidal properties (Leon-Sicairos et ah, 2006). The concentration of lactoferrin in milk has been reported as 1 g/liter in mature milk and 7 g/liter in colostrum (Houghton et ah, 1985). The concentration of lactoferrin in breast milk is controlled by the reproductive hormones prolactin and estrogen (Ward et ah, 2005). Lactoferrin has been demonstrated to resist digestion in the infant gut as it has been recovered intact from the stool of breast-fed infants (Bemt and Walker, 1999). Lactoferrin acts mainly in an iron-free state (apo-lactoferrin) and its microbicidal activity is reported to increase in proportion to its concentration in milk (Leon-Sicairos et ah, 2006). 

Hormones detected in milk include some from the peptide and steroid classes but none of the amino hormones. Prolactin, a protein of 199 amino acid residues, is normally present in a concentration of about 50 /tg/liter, and the hexapeptide gonadotropin-releasing hormone of the hypothalmus at about 1.5 g/liter. Steroid hormones from the adrenal cortex include the glucocorticoids cortisol and corticosterone, totaling 0.2-0.6 /tg/liter. Those from the ovary—progesterone, estrone, and estradiol—have concentrations of 10-30, 30, and 175 /ig/liter, respectively. Hormones in milk have been reviewed by Koldovsky (1980) and Pope and Swinburne (1980). The prolactin in milk is biologically active (Gala et al. 1980). 

As has been mentioned, in pigeons and doves the young are fed by a milk-like fluid regurgitated from the crop. This milk is formed by a sloughing of cells from the wall of the crop sac, a process which is stimulated by prolactin [96,97]. The hormone stimulates both an increase in proliferation of the cells which contribute to the milk and a change in the proteins and lipids contained within the cells [97,98], and these two types of response appear to be controlled independently [99]. The effect is a direct one, and prolactin can produce local effects when injected in the immediate vicinity of one side of the crop. 

Prolactin (PRL) Anterior Pituitary (Lactotroph) 198 aa (23 kDa) 6p22.2-q21.3 Stimulates growth and protein synthesis in breast promotes milk secretion during lactation. Primarily inhibited by PIH (dopamine) stimulated by PRF and TRH. 

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