Pseudophosphorylated prolactin (S179D PRL) inhibits growth and promotes beta-casein gene expression in the rat mammary gland.
We have investigated the individual roles of unmodified prolactin (U-PRL) and a mimic of phosphorylated PRL (S179D PRL) in mammary development. Recombinant versions of the PRLs were delivered to rats throughout pregnancy at a rate of 6 microg/24 h per rat and to non-pregnant females at a rate of 24 microg/24 h per rat. Measurement of progesterone, corticosterone, and estradiol showed no effect of the administered PRLs on the levels of these other mammotropic hormones. Histological and morphometric analysis showed U-PRL to cause mammary growth, whereas S179D PRL inhibited growth. Molecular analysis demonstrated decreased beta-casein expression in the mammary glands of the U-PRL-treated animals at term and increased beta-casein expression in the mammary glands of the S179D PRL-treated animals. Superior beta-casein gene expression in response to S179D PRL versus U-PRL was confirmed in HC11 cells. We conclude that U-PRL is important for growth, whereas S179D PRL promotes at least one measure of differentiated function in the mammary gland.
Kuo
C Benson
CB
Division of Biomedical Sciences, University of California, Riverside, CA 92521-0121, USA.
Wu
Wei
W
Xu
Xiaolei
X
Yang
Lili
L
Chen
Cyndi
C
Coss
Djurdjica
D
Birdsall
Ben
B
Nasseri
Dorsa
D
Walker
Ameae M
AM
D019943:Amino Acid Substitution; D000818:Animals; D002364:Caseins / Q000235:genetics*; D002455:Cell Division / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D004958:Estradiol / Q000097:blood; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008321:Mammary Glands, Animal / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010766:Phosphorylation; D011247:Pregnancy; D011374:Progesterone / Q000097:blood; D011388:Prolactin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology
D002364:Caseins; D011994:Recombinant Proteins; D011374:Progesterone; D004958:Estradiol; D011388:Prolactin; D003345:Corticosterone