EFFECTS OF GROWTH-HORMONE ON CHOLESTEROL-METABOLISM IN THE LACTATING RAT MAMMARY-GLAND

Lactating rats were treated for 48 h with bromocriptine (to inhibit pr olactin release) or bromocriptine together with an antiserum to rat GH . Animals given the combined treatment were also supplemented concurre ntly 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-gl utaryl-CoA reductase (HMG-CoA reductase), acyl-CoA:cholesterol acyltra nsferase (ACAT) and neutral cholesteryl ester hydrolase (CEH) and on t he microsomal concentrations of non-esterified and esterified choleste rol were measured. Lack of prolactin decreased HMG-CoA reductase but d id not affect ACAT, neutral CEH or the concentrations of microsomal ch olesterol or cholesteryl esters. In the absence of both hormones, an e ven greater reduction in HMG-CoA reductase together with increases in ACAT, neutral CEH and both of the microsomal sterols were observed. Co ncurrent supplementation with either bGH or hIGF-I wholly or partially prevented the effects on HMG-CoA reductase but only bGH was active ag ainst the increase in ACAT. Neither bGH nor hIGF-I could prevent the e ffects of the anti-hormone treatment on neutral CEH, and the changes i n ACAT and CEH activities were broadly reflected in the microsomal ste rol concentrations. The results indicate that the cessation of lactati on brings about rapid changes in the activities of the enzymes involve d in cholesterol metabolism within the mammary gland with a definite s witch from synthesis to storage. Supplementation with bGH alone was su fficient 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 h ad no effect on its conversion to the ester. On a whole-tissue basis, enzyme activities could be correlated with the physiological effects o f the anti-hormone treatments.