ABSTRACT

Rats in mid-lactation were treated, for 2 days, with anti-rat GH serum (anti-rGH) and/or bromocriptine before microsomes were prepared from the freeze-clamped mammary glands. The effects of these anti-hormone treatments on the concentrations of microsomal cholesterol and cholesterol esters and on the activities of acyl-CoA:cholesterol acyltransferase (ACAT), neutral cholesterol ester hydrolase and 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase) were measured. HMG-CoA reductase was determined in microsomes prepared in both the presence and absence of phosphatase inhibitors to determine the expressed and total activities respectively.

Anti-rGH reduced HMG-CoA reductase and increased microsomal cholesterol and cholesterol esters. Bromocriptine reduced HMG-CoA reductase but increased all of the other parameters. The results indicate that the initial stage in the stimulation of milk secretion involves a decrease in the activity of ACAT and that the phosphorylation level of HMG-CoA reductase is modulated by both prolactin and GH acting in opposition.

Journal of Endocrinology (1991) 128, 287–295

Lactating rats were treated for 48 h with bromocriptine (to inhibit prolactin release) or bromocriptine together with an antiserum to rat GH. Animals given the combined treatment were also supplemented concurrently with bovine GH (bGH) or human insulin-like growth factor-I (hIGF-I). The effects of these treatments on the activities of 3-methyl-3-glutaryl-CoA reductase (HMG-CoA reductase), acyl-CoA:cholesterol acyltransferase (ACAT) and neutral cholesteryl ester hydrolase (CEH) and on the microsomal concentrations of non-esterified and esterified cholesterol were measured.

Lack of prolactin decreased HMG-CoA reductase but did not affect ACAT, neutral CEH or the concentrations of microsomal cholesterol or cholesteryl esters. In the absence of both hormones, an even greater reduction in HMG-CoA reductase together with increases in ACAT, neutral CEH and both of the microsomal sterols were observed. Concurrent supplementation with either bGH or hIGF-I wholly or partially prevented the effects on HMG-CoA reductase but only bGH was active against the increase in ACAT. Neither bGH nor hIGF-I could prevent the effects of the anti-hormone treatment on neutral CEH, and the changes in ACAT and CEH activities were broadly reflected in the microsomal sterol concentrations.

The results indicate that the cessation of lactation brings about rapid changes in the activities of the enzymes involved in cholesterol metabolism within the mammary gland with a definite switch from synthesis to storage. Supplementation with bGH alone was sufficient to maintain cholesterol synthesis at control levels and could also significantly inhibit storage of the sterol as its ester. In the absence of GH, hIGF-I partially supported cholesterol synthesis but had no effect on its conversion to the ester. On a whole-tissue basis, enzyme activities could be correlated with the physiological effects of the anti-hormone treatments.

Journal of Endocrinology (1997) 152, 447–454