The amino-acid-derived polyamines have long been associated with cell growth and cancer, and specific oncogenes and tumour-suppressor genes regulate polyamine metabolism. Inhibition of polyamine synthesis has proven to be generally ineffective as an anticancer strategy in clinical trials, but it is a potent cancer chemoprevention strategy in preclinical studies. Clinical trials, with well-defined goals, are now underway to evaluate the chemopreventive efficacy of inhibitors of polyamine synthesis in a range of tissues.

/pdf/polyamines-and-cancer-old-molecules-new-understanding-3xbfwfrf9u.pdf

Polyamines and cancer: old molecules, new understanding

Arginine is a common substrate for the synthesis of nitric oxide and polyamines that are crucial for placental angiogenesis and growth in mammals. This study was conducted to test the hypothesis that dietary l-arginine supplementation may improve reproductive performance of pregnant gilts. Fifty-two pregnant gilts with body weight (BW) of 166.3 +/- 1.8 kg were housed individually in gestation crates. At d 30 of gestation, gilts were assigned randomly to corn-soybean-based diets supplemented with 1.0% L-arginine-HCl or 1.7% L-alanine (isonitrogenous control). Both diets contained 13.0 MJ metabolizable energy/kg and 12.2% crude protein and were fed to gilts at 1 kg twice daily during gestation. Backfat thickness and BW were measured and blood samples were obtained on 30, 70, 90, and 110 d of gestation. At d 110 of gestation, gilts were transferred to individual farrowing crates. The numbers of total piglets born and born alive, as well as birth weights of piglets, were recorded immediately after farrowing. Throughout the gestation, BW or backfat thickness of gilts did not differ between treatment groups. Plasma urea concentrations were lower in arginine-supplemented than in control gilts at d 90 (P < 0.010) and d 110 (P < 0.001) of gestation. Compared with the control group, arginine supplementation increased the number of pigs born alive by 22% (11.40 vs. 9.37, P = 0.032) and live litter birth weight of piglets by 24% (16.38 vs. 13.19 kg, P = 0.016). This exciting finding provides the first evidence for a marked increase of live-born piglets by 2 per litter through nutritional intervention in gilts.

/pdf/dietary-l-arginine-supplementation-enhances-the-reproductive-icpcnsncpl.pdf

Dietary L-arginine supplementation enhances the reproductive performance of gilts.

Ornithine decarboxylase: a key regulatory enzyme in normal and neoplastic growth.

Immunohistofluorescence studies of the rat central nervous system with antibodies to Phe-Met-Arg-Phe-NH2 (molluskan cardioexcitatory peptide) revealed a widespread neuronal system in the brain, spinal cord, and posterior pituitary. Immunoreactive axons and cell bodies were mainly located in cortical, limbic, and hypothalamic areas. Immunostaining of serial sections of the brain and pituitary showed that the Phe-Met-Arg-Phe-NH2 immunoreactive neurons were different from neurons labeled by antibodies to either Met-enkephalin or the putative Met-enkephalin precursor Tyr-Gly-Gly-Phe-Met-Arg-Phe, which is structurally related to Phe-Met-Arg-Phe-NH2. Control staining by antiserum absorption and radioimmunoassay indicated that the antibodies that caused the specific immunofluorescence recognized peptides with an amidated Arg-Phe sequence at the carboxyl terminus.

https://science.sciencemag.org/content/sci/214/4526/1248.full.pdf

Novel peptide neuronal system in rat brain and pituitary

The polyamines are ubiquitous polycationic compounds. Over the past 40 yr, investigation has shown that some of these, namely spermine, spermidine, and putrescine, are essential to male and female reproductive processes and to embryo/fetal development. Indeed, their absence is characterized by infertility and arrest in embryogenesis. Mammals synthesize polyamines de novo from amino acids or import these compounds from the diet. Information collected recently has shown that polyamines are essential regulators of cell growth and gene expression, and they have been implicated in both mitosis and meiosis. In male reproduction, polyamine expression correlates with stages of spermatogenesis, and polyamines appear to function in promoting sperm motility. There is evidence for polyamine involvement in ovarian follicle development and ovulation in female mammals, and polyamine synthesis is required for steroidogenesis in the ovary. Studies of the embryo indicate a polyamine requirement that can be met from maternal sources before implantation, whereas elimination of polyamine synthesis abrogates embryo development at gastrulation. Polyamines play roles in embryo implantation, in decidualization, and in placental formation and function, and polyamine privation during gestation results in intrauterine growth retardation. Emerging information implicates dietary arginine and dietary polyamines as nutritional regulators of fertility. The mechanisms by which polyamines regulate these multiple and diverse processes are not yet well explored; thus, there is fertile ground for further productive investigation.

/pdf/polyamines-on-the-reproductive-landscape-2vocdematk.pdf

Polyamines on the Reproductive Landscape

Gossypol acetic acid administered orally at 30 mg/kg body weight/day for five weeks inhibited the fertility of male rats without an apparent loss of libido. Sperm in the ejaculate were rendered immotile and were reduced in number. Serum testosterone and LH were reduced significantly from pretreatment values, whereas FSH values were not altered. Leydig cells from treated animals produced less testosterone than did control Leydig cells when incubated with LH. Furthermore, testosterone production by normal Leydig cells that were incubated with LH and gossypol was inversely related to gossypol concentration. Ultrastructural examination of epididymal spermatozoa revealed degeneration in the tail region, particularly in the mitochondrial sheath of the middle piece. Within the seminiferous epithelium, late spermatids displayed a similar degeneration, although not as severe. After a six-week recovery period, normal fertility was re-established and normal litters were produced. Sperm motility and number, serum testosterone and LH levels, and sperm structure all returned to normal.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/j.1939-4640.1981.tb00615.x

Young C. Lin

Papers

Effects of Gossypol on the Reproductive System of Male Rats

Ornithine decarboxylase activity and polyamine content of the placenta and decidual tissue in the rat

Diethylstilbestrol stimulates ornithine decarboxylase in kidney cells in culture

Dynamics of progesterone binding in nuclei and cytosol of estrogen-induced adenocarcinoma cells in primary culture.

Effects of age and 1,4,6-androsta-triene-3,17-dione on activities of hCG-induced 19-hydroxylase and aromatase of rat testes