Second messengers in the actions of prolactin

The nature of the mechanisms coupling binding of prolactin to its receptor at the plasma membrane to intracellular responses is poorly understood. The effects of the hormone are seen within the cell, including the nucleus, and a second messenger mechanism or its equivalent is therefore expected. Considerable effort has been devoted to investigating possible second messengers for prolactin [26,68,79,80], but there is little clear-cut evidence in favour of any one. 

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]. 

Cyclic GMP can have some prolactin-like actions in rat mammary tissue, including stimulation of RNA synthesis and elevation of levels of casein mRNA but not 

Cytoskeletal elements may also be involved in mediating the effects of prolactin on the mammary gland. Colchicine, which disrupts intracellular microtubules, completely blocks the effect of prolactin on casein mRNA production [86]. However, griseofulvin, another microtubule-disrupting drug, has no such effect. 

A series of studies has been reported suggesting that a messenger for the actions of-prolactin on mammary gland could be produced by incubating prolactin with mammary membrane preparations in vitro [87,88]. Partial purification of this putative messenger was reported, but the work proved difficult to repeat [89] and it is unclear whether the factor involved is a true prolactin messenger. 

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