FEMALE ENDOCRINE CONTROL MECHANISMS DURING THE NEONATAL PERIOD

1972 ◽  
Vol 70 (2) ◽  
pp. 396-408 ◽  
Author(s):  
K.-D. Schulz ◽  
H. Haarmann ◽  
A. Harland

ABSTRACT The present investigation deals with the oestrogen-sensitivity of the female reproductive system during the neonatal period. Newborn female guinea pigs were used as test animals. At different times after a single subcutaneous injection of a physiological dose of 0.1 μg or an unphysiologically high dose of 10 μg 17β-oestradiol/100 g body weight, the RNA- and protein-synthesis was examined in the hypothalamic region, pituitary, cerebral cortex, liver, adrenal gland, ovary and uterus. With a physiological dose an increase in organ weight, protein content, RNA-and protein-synthesis was found only in the uterus. These alterations turned out to be dose-dependent. In addition to the findings in the uterus an inhibition of the aminoacid incorporation rate occurred in the liver following the injection of the high oestradiol dose. As early as 1 hour after the administration of 0.1 μg 17β-oestradiol an almost 100% increase in uterine protein synthesis was detectable. This result demonstrates a high oestrogen-sensitivity of this organ during the neonatal period. All the other organs of the female reproductive system such as the hypothalamus, pituitary and ovary did not show any oestrogen response. Therefore the functional immaturity of the uterus during post partem life is not the result of a deficient hormone sensitivity but is correlated with the absence of a sufficient hormonal stimulus at this time. The investigation on the effects of actinomycin resulted in different reactions in the uterus and liver. In contrast to the liver a paradoxical actinomycin effect was found in the uterus after treatment with actinomycin alone. This effect is characterized by a small inhibition of RNA-synthesis and a 50% increase in protein synthesis. The treatment of the newborn test animals with actinomycin and 17β-oestradiol together abolished the oestrogen-induced stimulation of the uterine RNA-and protein-synthesis. Consequently, the effect of oestrogens during the neonatal period is also connected with the formation of new proteins via an increased DNA-directed RNA-synthesis.

1972 ◽  
Vol 71 (3) ◽  
pp. 431-442 ◽  
Author(s):  
K.-D. Schulz ◽  
A. Harland ◽  
H. Haarmann

ABSTRACT The present investigations deal with the in vivo effect of different doses of exogenous LH on the RNA- and protein-synthesis in the cerebral cortex, hypothalamus, pituitary, liver, ovary, uterus and adrenal gland of newborn guinea pigs. An increase of 3H-uridine and 3H-leucine incorporation was noted only in the ovary and the uterus. All the other organs showed no response. As early as 1 hour after the injection, LH induced a statistically significant stimulation of amino-acid incorporation into the proteins of the ovary. 2 hours later similar observations were made on the uterus reflecting an induction of uterotrophic steroid biosynthesis in the ovary in response to LH. The lowest effective dose was 5 IU LH/100 g body weight. Furthermore the experiments gave evidence for the dependence of oestrogen synthesis on the ovarian protein formation. The experimental data support the assumption that the ovary of newborn animals is not refractory to stimulation by gonadotrophic hormones. The ovary of newborn guinea pigs shows a relatively low sensitivity against RNA- and protein-synthesis inhibiting substances such as actinomycin and cycloheximide as compared to the liver. The mode of action of LH on the ovary seems to be identical during post partum life and advancing sexual maturation. The existing ovarian gonadotrophin sensitivity indicates that the hypothalamus or possibly the pituitary is primarily responsible for the functional immaturity of the endocrine ovarian control mechanisms during the neonatal period. The restricted functional capacity of the neonatal hypothalamus is characterized by the resistence of this organ to hormones regulating the hypothalamic endocrine function via short and long feedback mechanisms.


1973 ◽  
Vol 74 (1) ◽  
pp. 144-156 ◽  
Author(s):  
K.-D. Schulz ◽  
S. August

ABSTRACT The purpose of this paper is to report on the in vivo effect of different doses of cis- and trans-clomiphene on the RNA and protein synthesis in the ovary, liver, adrenal gland and uterus of newborn guinea pigs. After the sc injection of either isomer the biochemical parameters were determined at different time intervals. Both isomers induced an increase of the RNA- and protein-synthesizing activity in the uterus, but failed to do so in the ovary, liver and adrenal gland. According to data reported here and also by other investigators it may be assumed that the lack of ovarian response to the treatment with cis- or trans-clomiphene is primarily due to the functional immaturity of the female hypothalamus and/or pituitary during the neonatal period. Both isomers failed to modify the pattern of gonadotrophin release, as shown by the constancy of the ovarian RNA and protein synthesis after the administration of either of the isomers. In the uterus, both cis- and trans-clomiphene strikingly imitated the biochemical stimulation produced by natural oestrogens. In contrast to oestradiol-17β, both clomiphene isomers showed a later onset and longer duration of the oestrogenic activity. The first increase of the amino acid incorporation into uterine proteins was noted after 5 hours in the cis-clomiphene treated group and after 8 hours in the trans-clomiphene treated animals as compared to 1 hour when oestradiol-17β was used. This difference seems to be due to a delayed transfer of the cytoplasmic oestradiol receptor to the nucleus after the injection of cis- or trans-clomiphene. As compared to oestradiol-treated animals, the clomiphene injection provoked a prolonged elevation of the uterine protein-synthesizing activity, most likely reflecting an effect of the enterohepatic recirculation of both isomers.


2006 ◽  
Vol 50 (11) ◽  
pp. 3786-3792 ◽  
Author(s):  
Yan Q. Xiong ◽  
Arnold S. Bayer ◽  
Lisa Elazegui ◽  
Michael R. Yeaman

ABSTRACT Thrombin-induced platelet microbicidal protein 1 (tPMP-1) is a staphylocidal peptide released by activated platelets. This peptide initiates its microbicidal activity by membrane permeabilization, with ensuing inhibition of intracellular macromolecular synthesis. RP-1 is a synthetic congener modeled on the C-terminal microbicidal α-helix of tPMP-1. This study compared the staphylocidal mechanisms of RP-1 with those of tPMP-1, focusing on isogenic tPMP-1-susceptible (ISP479C) and -resistant (ISP479R) Staphylococcus aureus strains for the following quantitative evaluations: staphylocidal efficacy; comparative MIC; membrane permeabilization (MP) and depolarization; and DNA, RNA, and protein synthesis. Although the proteins had similar MICs, RP-1 caused significant killing of ISP479C (<50% survival), correlating with extensive MP (>95%) and inhibition of DNA and RNA synthesis (>90%), versus substantially reduced killing of ISP479R (>80% survival), with less MP (55%) and less inhibition of DNA or RNA synthesis (70 to 80%). Interestingly, RP-1-induced protein synthesis inhibition was equivalent in both strains. RP-1 did not depolarize the cell membrane and caused a relatively short postexposure growth inhibition. These data closely parallel those previously reported for tPMP-1 against this strain set and exemplify how synthetic molecules can be engineered to reflect structure-activity relationships of functional domains in native host defense effector molecules.


1976 ◽  
Vol 21 (2) ◽  
pp. 291-302
Author(s):  
C.J. Flickinger

Amoeba nuclear envelopes were damaged using microsurgery, and metabolic requirements for the steps in their repair were studied, and my placing the cells in a solution containing one of several metabolic inhibitors. The first step in repair, the association of pieces of endoplasmic reticulum with holes in the nuclear membranes, appears to be a passive process since it was not affected by inhibitors of energy production, RNA synthesis, or protein synthesis. In contrast, fusion of pieces of endoplasmic reticulum with the nuclear membranes at the margins of the holes was blocked by KCN and dinitrophenol, indicating that membrane fusion requires energy derived from respiration, but RNA and protein synthesis inhibitors did not prevent fusion of pieces of endoplasmic reticulum with the nuclear membranes. The subsequent completion of repair and restoration of intact nuclear membranes was almost completely blocked by inhibitors of respiration, and it was reduced in the presence of actinomycin and emetine, suggesting that in addition to a requirement for energy, some later steps in the repair of the nuclear membranes require RNA and protein synthesis.


1973 ◽  
Vol 59 (3) ◽  
pp. 615-623 ◽  
Author(s):  
P. R. Gabe ◽  
L. E. de Bault

Macromolecular syntheses in encysted Tetrahymena patula were studied using Feulgen fluorescence cytophotometry, autoradiography, and inhibitors of RNA and protein synthesis. Cycloheximide significantly depressed protein synthesis and D-actinomycin effectively blocked RNA synthesis. Under these conditions, the cells within the cyst were unable to divide. Both cytophotometric measurements and autoradiographic data with tritiated thymidine show that DNA synthesis does not occur during the encystment divisions. Excysted cells placed in nutrient broth medium showed a prolonged generation time after the first cell growth cycle, and by the third generation the mean DNA content per cell was almost triple that of starved excysted cells. These findings indicate that (a) the encystment divisions require RNA and protein synthesis, which are apparently effected through turnover, (b) the encystment division cycles occur in the absence of DNA synthesis, and (c) excysted cells placed in culture medium may go through more than one DNA replication per cell cycle.


1968 ◽  
Vol 46 (6) ◽  
pp. 903-906 ◽  
Author(s):  
L. Kazdová ◽  
T. Braun ◽  
P. Fábry ◽  
R. Poledne

RNA synthesis measured by the incorporation of orotic acid-6-14C into RNA was investigated in isolated adipose tissue of control rats and of rats adapted to periodic hyperphagia, evoked by meal-feeding (a single 2-h meal per day). Both groups were fasted for 22 h and subsequently fed a measured test meal for another 2 h. It was revealed that 2 and 4 h after feeding there was no significant change in comparison with values during fasting, whereas in tissue of meal-fed rats the specific activity of RNA gradually increased by 22% and 41% respectively. The difference between controls and meal-fed rats was even much more marked if the specific activity of RNA in fat cells, isolated after incubation of the tissue, was measured. A significantly greater response of meal-fed rats was found when protein synthesis and lipogenesis in adipose tissue were assessed under the same experimental conditions. The possibility is discussed that the enhanced RNA and protein synthesis in adipose tissue of meal-fed rats is associated with de novo synthesis of enzymes involved in adaptive hyperlipogenesis.


1965 ◽  
Vol 26 (3) ◽  
pp. 845-855 ◽  
Author(s):  
Ivan L. Cameron ◽  
E. Ernest Guile

Numerous nucleoli can be observed in the macronucleus of the logarithmically growing ciliated protozoan Tetrahymena pyriformis; at late log phase the nucleoli aggregate and fuse. In stationary phase this fusion process continues, leaving a very few large vacuolated nuclear fusion bodies in the nucleus. When these stationary phase cells are placed into fresh enriched proteose peptone medium, the large fusion bodies begin to disaggregate during the 2.5-hour lag phase before cell division is initiated. By 3 to 6 hours after inoculation the appearance of the nucleoli in many cells returns to what it was in logarithmic cells. In view of the possible role of nucleoli in ribosome synthesis, attempts were made to correlate the morphological changes to changes in RNA and protein metabolism. The beginning of an increased RNA synthesis was concomitant with the beginning of disaggregation of the large fusion bodies into nucleoli, which was noticed in some cells by 1 hour after the return to fresh enriched proteose peptone medium. Increased protein synthesis then followed the increased RNA synthesis by 1 hour. The supply of RNA precursors (essential pyrimidines) were removed from cultures which were grown on a chemically defined synthetic medium, in order to study the relation between nucleolar fusion and synthesis of RNA and protein. Pyrimidine deprivation drastically curtailed RNA and protein synthesis, but did not cause fusion of nucleoli. When pyrimidines were added back to this culture medium, RNA synthesis was immediately stimulated and again preceded an increased protein synthesis by 1 hour. These studies suggest the involvement of unfused nucleoli in RNA and protein synthesis and demonstrate the extreme plasticity of nucleoli with respect to changes in their environment.


1998 ◽  
Vol 17 (12) ◽  
pp. 661-667 ◽  
Author(s):  
Udo Ingbert Walther ◽  
Johannes Schulze ◽  
Wolfgang Forth

Inhalation of zinc fumes may lead to the acute respiratory distress syndrome. The mechanisms of pulmonary zinc toxicity are not yet understood. Therefore we investigated zinc-dependent depression of protein and RNA synthesis in rat and human lung cell lines. 1 After exposure to 120 or 150 mmol/l zinc, RNA synthesis as assessed by uridine incorporation decreased by 60-70% between 0 and 2 h exposition in rat alveolar type II cells (L2 cells) and human fibroblast-like cells (11Lu and 16Lu cells), and by 90% between 0 and 4 h in carcinoma-derived cells (A549 cells). 2 After 2 h exposure, L2, 11Lu, and 16Lu cells were half-maximally inhibited by 50 mmol/l zinc, whereas A549 cells were more resistant with half-maximal inhibition at 100 mmol/zinc. 3 Protein and RNA synthesis was inhibited in parallel in L2, 11Lu, and A549 cells as indicated by simultaneous determination of uridine and amino acid incorporation. In 16Lu cells, the decline in protein synthesis preceded RNA synthesis inhibition. Pretreatment with RNA synthesis inhibitors (amanitin or actinomycin D) had no effect on time curve and intensity of RNA synthesis inhibition. Taken together, our results indicate that the suppression of RNA and protein synthesis likely are independent phenomena, due to direct zinc effects on these biosynthetic pathways.


1982 ◽  
Vol 28 (6) ◽  
pp. 623-628 ◽  
Author(s):  
John P. Beilby ◽  
Dennis K. Kidby

A comparison of the kinetics of [1−14C]leucine and [2-14C]uracil incorporation into germinating spores of Glomus caledonius showed that RNA and protein synthesis had begun by 35 min after imbibition of water. Protein synthesis was essential for spore germination, and cycloheximide-sensitive protein synthesis occurred after the onset of germination. Early RNA synthesis was not affected by cycloheximide. Within 35 min of imbibition the tricarboxylic acid cycle, gluconeogenesis, and most amino acid biosynthetic pathways were operating.


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