EFFECT OF ACTINOMYCIN D ON THE PITUITARY RESPONSE TO LH-RH

1976 ◽  
Vol 81 (1) ◽  
pp. 73-81 ◽  
Author(s):  
Jesus A. Vilchez-Martinez ◽  
Akira Arimura ◽  
Andrew V. Schally

ABSTRACT The effect of Actinomycin D (Act D) on the release of LH and FSH induced by LH-RH was investigated in rats. Immature male rats received an iv infusion over a period of 3–4 h or a quick iv injection of synthetic LH-RH. Infusion of LH-RH significantly increased serum LH and FSH levels at 1, 2, 3 and 4 h after the initiation of infusion. Pre-treatment with 100 μg/100 g b. w. Act D failed to affect the rise of serum LH and FSH levels 1 h after the infusion but significantly suppressed the response at 2, 3 and 4 h. The increase in serum LH and FSH levels after a quick injection of LH-RH was unaffected by pre-treatment with Act D whether the antibiotic was injected 1 or 2 h before LH-RH. The results suggest that the initial phase of the pituitary response to LH-RH does not require DNA-dependent RNA synthesis, whereas that in the later period does. RNA synthesis may be necessary only to maintain the increased secretion of both LH and FSH during a continuous stimulation with LH-RH.

1977 ◽  
Vol 84 (2) ◽  
pp. 254-267 ◽  
Author(s):  
H. Edward Grotjan ◽  
Donald C. Johnson

ABSTRACT Follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone and androstenedione were measured by radioimmunoassays in the sera of immature male rats treated with luteinizing hormone-releasing hormone (LH-RH). A single dose of 10, 20, 40 or 80 ng of LH-RH produced a prompt increase in serum LH: significant changes in FSH were found only with the two larger doses. Serum testosterone increased to peak levels in 20 to 40 min and returned to control level by 120 min. Changes in androstenedione were temporally similar but smaller in magnitude. Four doses of 20 or 40 ng LH-RH given at 20 min intervals did not increase serum LH or testosterone concentrations above those found with a single injection; FSH was slightly higher after the fourth dose. However, 40 ng LH-RH given every 20 min for 2 h produced a dramatic increase in serum LH and FSH: serum and testicular androgens were also much higher during the second hour. A 2 h stimulation with 80 ng LH-RH given ip at 30 min intervals did not alter the response to the same treatment given 24 h later; i. e., neither the pituitary nor the gonad was primed by previous exposure to increased levels of LH-RH or gonadotrophins. These results suggest that a single pulse of LH-RH produces a predictable response in the animal, but multiple episodic stimuli produce variable responses: testes, on the other hand, produce androgens as long as gonadotrophins are available.


Blood ◽  
1972 ◽  
Vol 40 (5) ◽  
pp. 662-670 ◽  
Author(s):  
J. C. Schooley ◽  
L. J. Mahlmann

Abstract Significant increases in the serum erythropoietin of male rats occur after the end of a brief hypoxic exposure. These increases in the hormone are almost completely abolished when the kidneys are removed after the hypoxic exposure. Injection of puromycin or cycloheximide after the hypoxic exposure significantly decreases the subsequent increases in serum erythropoietin titers, whereas injections of actinomycin D at this time have no significant effect on erythropoietin levels. Injections of actinomycin D before the hypoxic exposure prevent the increase in serum erythropoietin that normally occurs. These findings suggest that a brief period of hypoxia initiates a DNA-dependent RNA synthesis that regulates the de novo ribosomal synthesis of protein(s) involved in the biogenesis of erythropoietin and that the kidney is essential for these reactions to occur.


2009 ◽  
Vol 21 (1) ◽  
pp. 211
Author(s):  
K.-C. Choi ◽  
T. T. B. Vo ◽  
E.-M. Jung ◽  
V. H. Dang ◽  
E.-B. Jeung

In a previous study, we demonstrated that although endocrine disruptors (EDs) with androgenic and anti-androgenic effects may alter reproductive function, their effects on the developing male reproductive organs may be distinct. To continue this line of study, we treated immature rats to examine the adverse effects of di-(2 ethylhexyl) phthalate (DEHP) and flutamide (Flu) on the male reproductive system. Immature male SD rats were treated daily with DEHP and/or Flu at postnatal day (PND) 21 to 35 in a dose-dependent manner, and the changes evoked by these EDs were determined by differences in male reproductive tract and other organ weights, testicular histology, and serum LH and testosterone levels in combination with global microarray analysis. Interestingly, the testes, prostate, seminal vesicle weight, and anogenital distances were significantly decreased in response to the highest dose of DEHP and Flu. There were no differences in serum LH and testosterone concentration at PND 35 for immature male rats exposed to DEHP and/or Flu. However, treatment with DEHP and/or Flu caused histopathological changes in testes in which the degeneration and denseness of germ cells and/or dilatation of the tubular lumen were observed in response to the high dose [500 mg kg–1 of body weight (BW)] of DEHP and medium dose (10 mg kg–1 of BW) of Flu. Additionally, the results from cDNA microarray indicated that 1272 genes were up-regulated (more than 2-fold) and 1969 genes were down-regulated in response to DEPH and/or Flu. These genes were identified based on their roles in some physiological processes (i.e. lipid and cholesterol homeostasis, steroidogenesis, sex determination, and calcium signal transduction). The significant decreases were observed in the expressions of steroidogenic genes (i.e. Star, Cyp11a1, or Hsd3b). In addition, a common set of targeting genes, including CaBP1, Vav2, Plcd1, Lhx1, and Isoc1, were altered following EDs exposure, suggesting a potential set of biomarker genes for screening anti-androgenic and/or androgenicity of EDs. Taken together, we demonstrated that exposure to DEHP and/or Flu resulted in a temporal alteration in gene expression profile in the testes of immature male rats, and their toxicological effects on male reproductive system are distinct depending on their anti-androgenicity, suggesting new insight into molecular mechanism(s) underlying detrimental impacts of EDs with anti-androgenic activities in human and wildlife.


1975 ◽  
Vol 79 (4) ◽  
pp. 658-662 ◽  
Author(s):  
Takeshi Yoshida ◽  
Yutaka Hattori ◽  
Hiroshi Hoshiai ◽  
Mutsuo Hirano ◽  
Katsuyuki Takahashi ◽  
...  

ABSTRACT In an experiment performed to investigate the effect of LH-RH on the anterior pituitary of rats, we studied the changes in the concentration of 3′,5′-cyclic AMP in the anterior pituitary and the uridine uptake by the anterior pituitary following the intravenous injection of 100 ng LH-RH. The results obtained are summarized as follows: 1) The tissue level of 3′,5′-cyclic AMP in the anterior pituitary reached the highest peak 15 min after the injection of LH-RH. 2) The uridine uptake of the anterior pituitary began to increase 15 min after the LH-RH injection and attained a maximum level (5 to 6 times the normal level) in 30 min. 3) The fact that the uridine uptake was inhibited to a considerable extent by the addition of actinomycin D to the incubation medium suggested that uridine was incorporated into the RNA fraction.


1975 ◽  
Vol 31 (10) ◽  
pp. 1235-1237
Author(s):  
M. A. Garcia-Hjarles ◽  
O. Vilar

1976 ◽  
Vol 83 (3) ◽  
pp. 493-505 ◽  
Author(s):  
H. L. Verjans ◽  
K. B. Eik-Nes

ABSTRACT Effect of intravenous administration of a synthetic gonadotrophin releasing factor (GnRF) on circulating LH and FSH concentrations was investigated in normal and gonadectomized, adult male rats injected subcutaneously each day during seven days with various doses of oestradiol-17β or 5α-dihydrotestosterone in sesame oil. Higher increase in serum LH and FSH levels subsequent to intravenously administered GnRF was observed in castrated control animals than in intact control animals, though this increment was not of significant nature for serum FSH. Pre-treatment of normal and gonadectomized rats with oestradiol-17β resulted in an augmented response of serum LH and FSH concentrations to GnRF iv. Pre-treatment of normal and gonadectomized rats with 5α-dihydrotestosterone diminished serum LH and FSH response following administration of the same amount of GnRF. For these steroids to affect the response pattern of serum LH and FSH to GnRF iv, higher doses were required in normal than in gonadectomized animals. The data indicate that oestrogen and androgen may act at different sites in the male hypothalamic-pituitary axis with respect to regulation of pituitary gonadotrophins.


2015 ◽  
Vol 40 (4) ◽  
pp. 615-622
Author(s):  
J. Buczek

Double-stranded DNA and in a lesser degree ATP reduce the inhibitory action of actinomycin D on auxin-induced elongation growth. The reduction of inhibition by DNA is significant in the initial phase of elongation up to the 4th hour of growth. The effect of ATP is similar but less pronounced. Both substances applied jointly do not completely abolish the inhibitory action of actinomycin D. The foregoing data and the kinetic characteristic of the auxin-induced elongation in the presence of actinomycin D suggest that this antibiotic inhibits growth by blocking synthesis of RNA essential for elongation growth and causes, moreover, certain distinct cellular changes which cannot be explained by the inhibition of DNA-depend RNA synthesis.


1976 ◽  
Vol 68 (1) ◽  
pp. 89-94 ◽  
Author(s):  
M. SHAHMANESH ◽  
S. L. JEFFCOATE

SUMMARY Rat stalk median eminence (SME) extract was incubated with various quantities of an antiserum raised against synthetic luteinizing hormone releasing hormone (LH-RH) and the resulting material was used at two or more dose levels to stimulate release of LH and FSH from anterior pituitary tissue, obtained from male rats, incubated in vitro. The resulting dose–response lines were used to obtain the LH- and FSH-releasing potency of the material, expressed as a percentage of SME extract pre-incubated with normal rabbit serum. Treatment with various doses of antiserum reduced LH-releasing and FSH-releasing potencies to a similar extent. Stalk median eminence extract and synthetic LH-RH were incubated with antiserum and directly compared in the same experiment in vitro. The changes in LH and FSH release caused by pre-treatment with antibody were similar for SME extract and synthetic LH-RH. In a final experiment, SME extract was passed through a column of Sepharose 2B particles to which was coupled anti-LH-RH antibody. The resulting material, when mixed with synthetic LH-RH and used to stimulate rat pituitary tissue in vitro caused a similar increase in the LH- and FSH-releasing potencies of the synthetic decapeptide. It is concluded that rat SME extract contains a single releasing factor for LH and FSH immunologically indistinguishable from synthetic LH-RH.


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