Changes in pituitary, hypothalamic and brain progestin-metabolizing enzyme activities during lactation.
Progesterone 5 alpha-reductase activity and 5 alpha-dihydroprogesterone 3 alpha-hydroxysteroid oxidoreductase (3 alpha-HSOR) activities (NADH- and NADPH-linked) were measured in anterior pituitaries, hypothalami and brains from lactating rats (8 and 21 days postpartum) and non-lactating (60-day-old cycling) rats. Tissue levels of these three enzyme activities varied significantly among the three groups examined. In terms of pituitary, mean levels of both of its 3 alpha-HSOR activities were 40-140% higher in actively lactating rats (8 days postpartum) relative to mean levels in lactating rats at weaning (21 days postpartum) or in non-lactating rats. There were no differences in pituitary progesterone 5 alpha-reductase activity among the three experimental groups. In the hypothalamus, the NADPH-linked 3 alpha-HSOR was elevated (50%) at 8 days of lactation compared to the group at 21 days. Hypothalamic NADH-linked 3 alpha-HSOR levels did not vary among the 3 groups. Hypothalamic progesterone 5 alpha-reductase levels in the actively lactating and weaning groups were 30% lower than those of the non-lactating group. Brain levels of progesterone 5 alpha-reductase were also lower in these two lactating groups (35-55%) as compared to the non-lactating control group. In brain, NADPH 3 alpha-HSOR activity did not vary among the three groups, but levels of NADH 3 alpha-HSOR activity were lower (40-50%) in the weaning group as compared to the actively lactating and control groups. These findings suggest the possibility that tissue changes in these progesterone-metabolizing enzyme activities during lactation and at weaning are influencing the in situ supply of 3 alpha,5 alpha-tetrahydroprogesterone and 5 alpha-dihydroprogesterone and their derivative effects on GABAA receptor activity and prolactin and gonadotropin release. The decreased activity of progesterone 5 alpha-reductase in hypothalamus and brain would presumably reduce in situ 5 alpha-dihydroprogesterone formation while increases in 3 alpha-HSOR activity would suggest higher in situ 3 alpha,5 alpha-tetrahydroprogesterone formation, especially in the pituitary.
Karavolas
H J
HJ
Department of Biomolecular Chemistry, University of Wisconsin-Madison 53706.
Hodges
D R
DR
D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific); D000818:Animals; D001921:Brain / Q000201:enzymology*; D005260:Female; D007031:Hypothalamus / Q000201:enzymology*; D007774:Lactation / Q000502:physiology*; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D010903:Pituitary Gland, Anterior / Q000201:enzymology*; D011372:Progestins / Q000378:metabolism*; D051381:Rats; D013997:Time Factors
D011372:Progestins; D009243:NAD; D009249:NADP; D010088:Oxidoreductases; D015096:3-Hydroxysteroid Dehydrogenases; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific); C022447:3-oxo-5-alpha-steroid 4-dehydrogenase (NADP(+))