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D J Flint

Publications and source records attributed to D J Flint.

120 records · Page 7Linked to original sources

Regulation of adipocyte insulin receptor number and metabolism during late-pregnancy.

The regulation of the rate of fatty acid synthesis of rat adipose tissue during late-pregnancy has been investigated. Rats at day 18 of pregnancy were injected over a 2-day period with either prostaglandin F2 alpha (PGF2 alpha), PGF2 alpha plus progesterone, PGF2 alpha plus bromocriptine or carrier solutions, and were then killed on day 20 of pregnancy. Injections of PGF2 alpha resulted in a decreased rate of fatty acid synthesis, a lower serum-insulin concentration, and a reduced number of insulin receptors of adipocytes. Concurrent injections of progesterone, but not of bromocriptine, along with the PGF2 alpha prevented these effects of the latter. The results are consistent with our previous suggestion that the fall in serum progesterone concentration prior to parturition results in a reduction in the number of insulin receptors of adipocytes, which, along with a fall in the serum-insulin concentration, leads to a decrease in the anabolic activity of the tissue.

Adipose Tissue↗

Effects of prolactin and the suckling stimulus on implantation and LH secretion in rats.

Litter removal during lactation led to an increase in serum LH concentration, an effect which was completely reversed by prolactin injections. Lactating rats receiving ergocryptine also showed increased serum LH but not to the extent found during litter removal, suggesting that both prolactin and suckling are important factors in the maintenance of lactational anoestrus. The early implantation induced by removal of the litter from rats concurrently lactating and pregnant was not prevented by prolactin. Implantation occurred early in similar rats with serum prolactin levels reduced by ergocryptine treatment and the effect was reversed by prolactin. However, early implantation led to failure of the pregnancy to reach term. These results show that, although prolactin is involved, the suckling stimulus is also essential to prevent implantation in rats with concurrent lactation and pregnancy.

Animals↗

Role of insulin receptors in the changing metabolism of adipose tissue during pregnancy and lactation in the rat.

Changes in the volume, the rates of fatty acid synthesis and synthesis of the glycerol moiety of acylglycerols, the activity of lipoprotein lipase, and the number and affinity of insulin receptors of adipocytes, and concentrations of serum insulin, prolactin and progesterone were determined in virgin rats and in rats at various stages of pregnancy and lactation. Changes in the metabolic activities of adipose tissue appeared to be synchronized and primarily comprised a marked decrease in anabolic activity around parturition. In contrast, the number of insulin receptors (Kd 1.5 nM) per adipocyte doubled during pregnancy before returning to normal values around parturition. It is postulated that the increase in the number of insulin receptors is an adaptation to counteract the effects of insulin-antagonistic hormones during pregnancy and that the decrease in the number of receptors is primarily responsible for the loss of anabolic activity around parturition.

Adipose Tissue↗

Effects of ergocryptine on prolactin secretion druing concurrent pregnancy and lactation in the rat.

Ergocryptine (2 mg/kg) caused short- and long-term reduction of prolactin secretion in rats experiencing concurrent lactation and pregnancy. The long-term effects of the drug lasted at least 60 days and resulted in reduced milk secretion and termination of pregnancy. Prolactin replacement therapy at a low dose (5 i.u./day) was unsuccessful in overcoming these effects but a higher dose (up to 60 i.u./day) increased milk production and maintained pregnancy. One possible explanation of these results is that prolactin, rather than the suckling stimulus, was responsible for the suppression of oestrous cycles, because ergocryptine brought about a resumption of oestrous vaginal smears in all treated rats in spite of continued suckling.

Animals↗

Identification of chicken (Gallus domesticus) adipocyte plasma membrane and differentiation specific proteins using SDS-PAGE and western blotting.

1. Affinity-purified adipocyte membrane proteins were used to raise antisera in two sheep. 2. Using one of the antisera 15 proteins were identified as being adipocyte specific by comparison on Western blots of plasma membrane proteins from various tissues. 3. Of these 15 proteins eight appeared to be present only in mature adipocytes and not in the adipocyte precursor. 4. In the presence of guinea pig complement the two antisera raised were cytotoxic to adipocytes and their precursors. 5. Characterization and further study of these adipocyte differentiation specific proteins will provide valuable information about the process of adipocyte differentiation.

Adipose Tissue↗

Modulation of the actions of IGFs by IGFBP-5 in the mammary gland.

IGFBP-5 has been associated with cell death in a number of systems; recently, the first evidence that it is involved in apoptosis of the mammary gland has been provided by studies, both in vivo and in vitro, involving the addition of exogenous IGFBP-5 and from a transgenic mouse expressing IGFBP-5 on a mammary-specific promoter. These studies have indicated that the effects are mediated in part by inhibition of IGF-signalling and involving members of the Bcl-2 family, but a role for IGF-independent effects cannot be ruled out. These IGF-independent effects involve potential interactions with components of the extracellular matrix involved in tissue remodelling such as components of the plasminogen system. In addition, intracellular events involving nuclear localisation of IGFBP-5 have been shown to have potential to inhibit cell proliferation. IGFBP-5 binds to a considerable number of molecules in the extracellular matrix, but the specific roles of these interactions in modulating its biological effects are poorly understood. The development of IGFBP-5 mutants, with differential binding characteristics, will aid in elucidating the precise roles of IGFBP-5 and potentially offer new therapeutic approaches based on IGF-independent effects in addition to its classical role of modulating IGF actions.

Animals↗