In vivo synthesis of phosphatidylcholine in rat brain via the phospholipid methylation pathway.

We examined the in vivo synthesis of brain phosphatidylcholine (PC) by the methylation of phosphatidylethanolamine (PE). [3H-methyl]methionine was infused i.c.v., by indwelling cannula, and brain samples were taken 0.5-18 h thereafter and assayed for [3H]PC, as well as for its biosynthetic intermediates [3H]phosphatidylmonomethylethanolamine ([3H]PMME) and [3H]phosphatidyldimethylethanolamine ([3H]PDME), and for [3H]lysophosphatidylcholine ([3H]LPC) and S-[3H]adenosylmethionine ([3H]SAM). Most of the [3H]PC (79-94%) was present ipsilateral to the infusion site, indicating that the radioactivity in the [3H]PC was primarily of intracerebral origin, and not taken up from the blood. Moreover, only very low levels of [3H]PC were attained in brains of animals receiving [3H]methionine i.p. and these levels were symmetrically distributed. [3H]PMME and [3H]PDME turned over with apparent half-lives of 2.2 h and 2.4 h. In contrast, the accumulation of brain [3H]PC was biphasic, suggesting the existence of two pools, the more labile of which turned over rapidly (t1/2 = 5 h) and was formed for as long as [3H]PMME and [3H]PDME are present in the brain, and another, which was distinguishable only at 18 h after the [3H]methionine infusion. (The latter pool may have been synthesized from [3H]choline that was released via the hydrolysis of some of the brain [3H]PC previously formed by the methylation of PE.) Subcellular fractionation of brain tissue obtained after in vivo labelling with [3H]methionine revealed that mitochondrial PC had the highest specific radioactivity (dpm per mumol total lipid phosphorus), and myelin the least. These observations affirm that rat brain does synthesize PC in vivo by methylating PE, and the technique provides an experimental system which may be useful for examining the physiological regulation of this process.

Molecular composition of the phosphatidylcholines produced by the phospholipid methylation pathway in rat brain in vivo.

We examined the formation in vivo of molecular subspecies of brain phosphatidylcholine (PC) via the phospholipid-methylation pathway. [3H]Methionine was infused into a lateral cerebral ventricle, and 3H-labelled PC was isolated from brains of rats 0.1-18 h after the infusions. Three major subspecies of this PC, differing in their fatty acid compositions, were separated on silver-impregnated t.l.c. plates, and the proportions of radioactivities in these three PC fractions were determined. The results indicate that newly-formed PC synthesized by methylation of phosphatidylethanolamine at 0.1 h after [3H]methionine contains a significantly higher proportion of polyunsaturated subspecies (i.e. those with six or four double bonds) than does PC obtained later times after injection of [3H]methionine. This change in the composition of 3H-labelled brain PC occurs gradually and is not due to an influx of radioactive PC from the periphery. Our data suggest that polyunsaturated PC (hexaenes and tetraenes) produced in the brain by methylation of phosphatidylethanolamine turns over faster than does that containing more-saturated fatty acids.

Formation and degradation of deamido-TRH (pyroglutamyl-histidyl-proline) in rat brain after intraventricular injection of TRH.

Thyrotropin-releasing hormone (TRH) injected into the lateral ventricle of the rat's brain was rapidly metabolized to deamido-TRH (DA-TRH). Brain levels of TRH decreased with a half-life of 7 min, while the DA-TRH formed from its disappeared with a half-life of 2.5 min. To prevent the post-mortem degradation of DA-TRH it was necessary to sacrifice rats by directing focused microwave irradiation towards the brain. The short half-lives determined for TRH and DA-TRH in vivo were much shorter than those obtained using in vitro techniques. The in vivo formation and accumulation of DA-TRH was inhibited by bacitracin and unaffected by probenicid.

[Hormonal status and the clinical course of ovarian cancer]. / Gprmonal'nyi status i klinicheskoe techenie raka iaichnikov.

PIP: As a rule, patients with ovarian cancer do not display any important endocrine disturbances. The authors studied the cases of 104 of these patients: 19 had benign tumors, 6 intermediate tumors, 6 had 1st stage ovarian cancer, 7 3rd stage cancer, 54 4th stage cancer. The remaining patients had a recidivist ovarian cancer. All patients with primary cancer had the uterine hormonal secretions studied. The results indicated the absence of specific changes in the uterine secretion of steroid hormones and in the level of follicle stimulating hormone and luteinizing hormone in the serum. This was true for all patients with benign, intermediate and malignant ovarian tumors. The duration of remission in the patients with 4th stage of cancer was greater when the estrogen stimulation and the level of androgen secretion were increased.^ieng