Effects of prenatal administration of mestranol and two progestins on testosterone synthesis and reproductive tract development in male rats

1987 ◽  
Vol 116 (2) ◽  
pp. 193-199 ◽  
Author(s):  
Santosh K. Varma ◽  
Eric Bloch

Abstract. The oestrogen mestranol (0, 0.01, 0.1 mg/kg body weight per day) and the progestins medroxyprogesterone-acetate and norethisterone (0, 2, 20 mg/kg body weight per day each) in sesame oil were intubated intragastrically daily during gestational days 14.5 through 19.5 to pregnant rats. Males were studied as 20.5-day-old foetuses and 4-month-old adults for serum testosterone and LH concentrations, in vitro testosterone synthesis, anogenital distance (foetuses only) and testes, seminal vesicle and ventral prostate weights. Administration of 0.1 mg mestranol decreased by 35 to 70% basal and LH-stimulated testosterone synthesis by both foetal and adult testes in vitro (P < 0.01). Foetal body weights (P < 0.05), but not anogenital distances, were significantly decreased. Testosterone content in adult sera was reduced significantly (P < 0.05) to less than 50% of control. Testes, ventral prostate, seminal vesicle and epididymal weights were unaffected by treatment. Medroxyprogesterone acetate or norethisterone administration did not alter testes endocrine function in foetal or adult offspring. In a small number of rats, pregnant for 10.5, 14.5 or 18.5 days, [3H]ethinyloestradiol was intubated and foetal and placental tissue examined for appearance and content of radioactivity. Radioactivity was detected in 10.5, 14.5 and 18.5 days old placentas, and 14.5 and 18.5 days old foetal liver, gonads and external genitalia. With [3H]medroxyprogesterone acetate, radioactivity was localized in 14.5 day placenta and foetal tissues. Thin-layer chromatographic analysis showed most of the activity to migrate as authentic ethinyloestradiol or medroxyprogesterone acetate. The results demonstrate inhibition of testicular testosterone synthesis by mestranol, presumably by being transferred across the placenta and acting in the foetus. The diminished activity of adult testes indicates a permanent effect of in utero mestranol exposure on testes function.

1995 ◽  
Vol 14 (11) ◽  
pp. 889-894 ◽  
Author(s):  
N. Pant ◽  
AK Prasad ◽  
SC Srivastava ◽  
R. Shankar ◽  
SP Srivastava

1 Carbofuran was administered orally to adult male rats at dose levels of 0.1, 0.2, 0.4 or 0.8 mg kg -1 body weight, 5 d wk-1 for 60 days. A dose dependent decrease was observed in body weight of rats treated with 0.2-0.8 mg carbofuran kg -1 body weight 2 A significant decrease in the weight of epididymides, seminal vesicles, ventral prostate and coagulating glands was observed at various test doses of carbofuran except at the lowest dose. 3 Decreased sperm motility, reduced epididymal sperm count along with increased morphological abnormali ties in head, neck and tail regions of spermatozoa were observed in rats exposed to 0.2, 0.4, or 0.8 mg carbo furan kg-1 body weight. 4 In addition, significant alterations were observed in the activities of marker testicular enzymes viz. sorbitol dehydrogenase (SDH), glucose-6-P-dehydrogenase (G6PDH) (decreased), lactate dehydrogenase (LDH) and γ-glutamyl transpeptidase (γ-GT) (increased) depending on dose. 5 Histologically, the results indicated the toxicity of carbo furan on testes depending on dose. The changes pre dominantly consisted of moderate oedema, congestion, damage to Sertoli cells and germ cells, along with the accumulation of cellular debris and presence of giant cells in the lumen of a few seminiferous tubules which showed disturbed spermatogenesis with the higher doses of carbofuran. 6 These observations determined a no effect level dose of 0.1 mg kg-1 body weight of carbofuran on the biochemi cal and morphological indices studied for male repro ductive toxicity assessment in the rat model. The results of the present study provide first hand information on the reproductive toxicity of carbofuran in male rats.


Author(s):  
Adetutu Adewale ◽  
Olaniyi Deborah Temitope ◽  
Awodugba Tamilore ◽  
Owoade Abiodun Olusoji ◽  
Olaniyan, Lamidi Waheed B. ◽  
...  

Typhoidal salmonella infections remain a challenge in the health care system in sub-Saharan Africa. Carrier status and advent of multi-drug resistant S. Typhi strains have necessitated the search for new drug leads. Hence, this study aims at investigating P. guajava and A. indica leaves for anti-salmonella activities. Guava and neem leaves were extracted by maceration in methanol and fractionated by solvent partitioning. In vitro activities were assessed by agar well diffusion and broth micro-dilution methods. Sixty male rats were randomized to 10 groups of 6 animals each for the in vivo experiments. Groups of rats except, normal control, were induced with 0.5McFarland of S. Typhi suspension orally. Treatment groups received 200 mg/kg body weight of extracts and fractions, and the control groups were treated with 14.29mg/kg body weight of ciprofloxacin and 1%v/v DMSO for 7 days post-infection. Biochemical parameters were determined spectrophotometrically. Hematological parameters were analyzed with automated hematology diagnostic machine. All fractions of P. guajava and three of A. indica inhibited S. Typhi growth with Zone of Inhibition (ZI) ranging from 11-15 mm. Active fractions inhibited 48.60-62.45% of S. Typhi biofilm formation at 25 mg/mL with Minimum Bactericidal Inhibitory Concentration (MBIC) of 0.39-12.5 mg/mL. All fractions improved body weight of treated rats and inhibited bacteremia at 44.75 and 95.94%. Hematological parameters improved in all fractions-treated rats. MDA was not significantly (p<0.05) altered in all groups. One fraction of P. guajava (ePg) lowered the elevated level in concentration of Nitric oxide (NO) while all fractions enhanced the lowered activity of SOD. Elevated (lactate dehydrogenase (LDH), aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and bilirubin (BIL) were lowered by all fractions to various extents in treated rats. Fractions of P. guajava, and A. indica could be further considered for identification of active anti-salmonella principle(s).


1992 ◽  
Vol 132 (3) ◽  
pp. 449-459 ◽  
Author(s):  
B. Pérez-Villamil ◽  
E. Bordiú ◽  
M. Puente-Cueva

ABSTRACT We have investigated the role of physiological prolactin levels in the development of prepubertal male rats. Prolactin GH and testosterone levels, as well as body, ventral prostate and testicular weight, have been analysed in both control and bromocriptine-treated rats between 21 and 60 days of life. Furthermore the role of prolactin in the regulation of its own receptors has also been studied during the same period. In control rats, prolactin levels showed a prepubertal peak of secretion at 25 days of age. At this time GH and testosterone levels were low and did not show any significant variation. After this age, prolactin levels increased more gradually; determinations of GH showed great variation with low levels in most of the rats and very high values in the other animals; testosterone levels remained low until day 35 after which they increased. Simultaneously with the serum prolactin peak on day 25, a decrease in prolactin-binding capacity of ventral prostate glands, was observed and a maximum rate of body, prostate and testicular weight gain was obtained. Furthermore, in rats with pharmacologically suppressed serum prolactin levels (lower than 1 μg/l), prolactin binding to prostate glands as well as the weight of body, ventral prostate and testes were lower than in control animals. When results were expressed in mg prostate or testes/g body weight, testes from 25-day-old treated rats weighed significantly less than controls. The later stages of development, from days 25 to 60, were characterized by an initial decline in serum prolactin levels at 29 days of age which was followed by a continuous increase until adult values were reached. During this period, prostatic prolactin receptors which were at their lowest value at 33 days of age showed a gradual rise parallel with the observed increase in plasma prolactin levels. When testicular tissue was analysed, no changes in prolactin-binding sites caused by sexual maturation were observed. The present results indicate that physiological prolactin secretion has a specific effect on the normal increase in the prostate, testes and body weight and clearly is also implicated in the regulation of its prostatic receptors at the earlier stages of development. Journal of Endocrinology (1992) 132, 449–459


Author(s):  
М. Голубева

Введение. Изменение реологических свойств крови характерно для различных заболеваний, многие из которых связаны с нарушением реологии и, прежде всего, с изменением агрегации эритроцитов. Целью исследования было сравнение влияния малых регуляторных пептидов, являющихся фрагментами нейрогормонов, на агрегацию эритроцитов и тромбоцитов под действием адреналина в экспериментах in vitro. Материалы и методы. Эксперименты проводили на белых беспородных крысах-самцах, массой тела 180-200 г. Использовали пептиды, представляющие собой С-концевые фрагменты вазопрессина (Pro-Arg-Gly-NH2) и окситоцина (Pro-Leu-Gly-NH2). Результаты. Показано, что малые регуляторные пептиды, являющиеся продуктами протеолиза нейропептидов, оказывают существенное влияние на агрегатное состояние клеток крови. При сравнении влияния пептидов на агрегацию клеток крови, стимулированную адреналином, установлено, что фрагмент вазопрессина Pro-Arg-Gly-NH2 вызывал достоверное усиление агрегации как эритроцитов, так и тромбоцитов; тогда как фрагмент окситоцина Pro-Leu-Gly-NH2 ингибировал только агрегацию эритроцитов, не изменяя агрегации тромбоцитов. Заключение. Изучение путей поэтапного протеолиза пептидов может привести к разработке новых препаратов для направленной коррекции различных нарушений в организме, поэтому изучение эффектов С-концевых фрагментов гипофизарных гормонов на гемостаз является актуальным. Introduction. The changing of blood rheological properties is typical for various diseases; many of them are associated with rheology disorder and primarily with change of erythrocytes aggregation. The aim was to compare the effect of small regulatory peptides (fragments of neurohormones) on the aggregation of erythrocytes and platelets under adrenaline action in experiments in vitro. Materials and methods. Experiments were conducted on white outbred male rats, body weight 180-200 g. We used 2 peptides – C-terminal fragments of vasopressin (Pro-Arg-Gly-NH2) and oxytocin (Pro-Leu-Gly-NH2). Results. It was shown that small regulatory peptides (they are products of neuropeptides proteolysis) had a significant effect on blood cells aggregation. We compared the peptides effect on blood cells aggregation stimulated by adrenaline. It was found that vasopressin fragment Pro-Arg-Gly-NH2 significantly increased both erythrocytes and platelets aggregation, while oxytocin fragment Pro-Leu-Gly-NH2 inhibited only erythrocytes aggregation without changing of platelet aggregation. Conclusion. Investigation of phased peptides proteolysis may result in the development of new drugs for targeted correction of various disturbances. So it is of current interest to study the effects of C-terminal fragments of pituitary hormones on hemostasis.


2000 ◽  
pp. 406-410 ◽  
Author(s):  
M Tena-Sempere ◽  
L Pinilla ◽  
LC Gonzalez ◽  
J Navarro ◽  
C Dieguez ◽  
...  

The obese gene (ob) product, leptin, has recently emerged as a key element in body weight homeostasis, neuroendocrine function and fertility. Identification of biologically active, readily synthesized fragments of the leptin molecule has drawn considerable attention, as they may provide a powerful tool for detailed characterization of the biological actions of leptin in different experimental settings. Recently, a fragment of mouse leptin protein comprising amino acids 116-130, termed leptin(116-130) amide, was shown to mimic the effects of the native molecule in terms of body weight gain and food intake, and to elicit LH and prolactin (PRL) secretion in vivo. As a continuation of our previous experimental work, the present study reports on the effects of leptin(116-130) amide on basal and stimulated testosterone secretion by adult rat testis in vitro. In addition, a comparison of the effects of human recombinant leptin and leptin(116-130) amide at the pituitary level on the patterns of LH, FSH, PRL and GH secretion is presented. As reported previously by our group, human recombinant leptin(10(-9)-10(-7)M) significantly inhibited both basal and human chorionic gonadotrophin (hCG)-stimulated testosterone secretion in vitro. Similarly, incubation of testicular tissue in the presence of increasing concentrations of leptin(116-130) amide (10(-9)-10(-5)M) resulted in a dose-dependent inhibition of basal and hCG-stimulated testosterone secretion; a reduction that was significant from a dose of 10(-7)M upwards. In addition, leptin(116-130) amide, at all doses tested (10(-9)-10(-5)M), significantly decreased LH and FSH secretion by incubated hemi-pituitaries from adult male rats. In contrast, in the same experimental protocol, recombinant leptin(10(-9)-10(-7)M) was ineffective in modulating LH and FSH release. Finally, neither recombinant leptin nor leptin(116-130) amide were able to change basal PRL and GH secretion in vitro. Our results confirm the ability of leptin, acting at the testicular level, to inhibit testosterone secretion, and map the effect to a domain of the leptin molecule that lies between amino acid residues 116 and 130. In addition, we provide evidence for a direct inhibitory action of leptin(116-130) amide on pituitary LH and FSH secretion, a phenomenon not observed for the native leptin molecule, in the adult male rat.


1971 ◽  
Vol 51 (2) ◽  
pp. 241-NP ◽  
Author(s):  
H. H. FEDER

SUMMARY 5α-Androstan-17β-ol-3-one in its free or in its propionate form was injected systemically (125 μg/day/rat) into sexually experienced, adult, castrated, male rats. These compounds were ineffective in activating masculine behaviour patterns, despite having measurable effects on body weight, seminal vesicle weight and penile morphology. The propionate form also had strong anti-gonadotrophic properties, since when it was injected for 6 days into intact, immature, male rats it significantly reduced testicular weight. In contrast, testosterone propionate (125 μg/day/rat) restored male sexual behaviour to the levels found before castration when injected systemically. Testosterone propionate also affected body weight, seminal vesicle weight, penile morphology and the testicular weight of immature males. These effects may have been due in part to conversion of testosterone to 5α-androstan-17β-ol-3-one, but this metabolic step does not seem to be obligatory for activation of male sexual behaviour in rats.


1982 ◽  
Vol 95 (3) ◽  
pp. 311-313 ◽  
Author(s):  
Vladimir Petrow ◽  
G. M. Padilla ◽  
Keith Kendle ◽  
A. Tantawi

6-Methylene-4-pregnene-3,20-dione, a potent irreversible inhibitor of rat prostate 5α-reductase in vitro, markedly inhibited the growth of the ventral prostate and seminal vesicles in immature rats when administered s.c. in a daily dose of 100 mg/kg body weight for 35 days. Kidney and testes weights were reduced, together with some reduction in body weight. In the mature rat treated with this steroid in a dose of 40 mg/kg body weight per day for 11 days, marked regression in ventral prostate and seminal vesicles was observed.


The Prostate ◽  
1987 ◽  
Vol 11 (4) ◽  
pp. 361-375 ◽  
Author(s):  
M. Fathy El Etreby ◽  
Ursula-F. Habenicht ◽  
Thomas Louton ◽  
Yukishige Nishino ◽  
Helmut G. Schröder

1965 ◽  
Vol 49 (1) ◽  
pp. 145-154 ◽  
Author(s):  
Fred A. Kind ◽  
M. Maqueo ◽  
Ralph I. Dorfman

ABSTRACT Various neutral steroids were studied in intact male rats for their ability to influence testicular function, particularly spermatogenesis. The compounds were injected once daily for 21 days, starting at 21 days of age. One day after the last injection, testicular histology and testis, ventral prostate, and seminal vesicle weights were determined. In some experiments, after the standard 21 day treatment period, testicular histology and function were evaluated after 30 and 60 day post-treatment recovery periods. 2α-Hydroxymethyl-17β-hydroxy-5α-androstan-3-one, 2-hydroxy-5α-androst-2-en-17β-ol, 2,17α-dimethyl-5α-androst-2-en-17β-ol and 2-formyl5α-androst-2-en-17β-ol caused decreases in testicular, ventral prostate and seminal vesicle weight and produced arrest of spermatogenesis. These effects were reversible and testis weight and histology, as well as fertility, were restored in the post-treatment period. 19-Norprogesterone, which did not produce convincing testicular atrophy, did cause significant decreases in ventral prostate and seminal vesicle weight. Chlormadinone showed a similar picture, although direct antagonistic testicular effects were also seen. The lowered ventral prostate and seminal vesicle weights produced by these compounds may be an expression of their antiandrogenic activity.


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