scholarly journals The effects of testosterone and oestrogen on gonadectomised and intact male rat anterior pituitary mitotic and apoptotic activity

2006 ◽  
Vol 188 (3) ◽  
pp. 387-396 ◽  
Author(s):  
L A Nolan ◽  
A Levy

We have used a direct, non-immunochemical and highly accurate method to quantify the effects of testosterone and oestrogen on mitotic and apoptotic activity in the young, male rat anterior pituitary in vivo. Surgical gonadectomy resulted in a 3-fold increase in mitotic activity by the fourth post-operative day, which returned gradually to levels seen in intact animals over the subsequent 3–4 weeks. Both a single dose of Sustanon, a mixture of long-acting testosterone esters in arachis oil, and the same dose divided over 7 days (starting 6 days after gonadectomy), initially suppressed mitotic activity to levels seen in intact animals, but was associated after 48–96 h with a wave of increased mitotic activity. The latter was blocked by co-administration of Sustanon with the non-steroidal aromatase inhibitor letrozole and was not seen when the non-aromatisable androgen dihydrotestosterone was substituted for Sustanon. Oestrogen alone in gonadectomised and intact rats produced a marked increase in mitosis as expected. With the exception of a transient increase in response to a single high-dose injection of Sustanon in gonadectomised animals, apoptotic activity was unaffected by all of the above. This study suggests that pituitary mitotic activity is tonically inhibited by gonadal hormone production (at least in the short term) in adult male rats. The study also suggests that supraphysiological testosterone treatment – while unable to reduce anterior pituitary mitotic activity in untreated, intact animals –suppresses the early increase in mitotic activity induced by gonadectomy. Oestrogen, either exogenous or generated locally by aromatisation, stimulates anterior pituitary mitotic activity in a time-dependent manner.

1981 ◽  
Vol 59 (10) ◽  
pp. 1082-1088 ◽  
Author(s):  
G. R. Cooper ◽  
S. H. Shin

Somatostatin inhibits not only growth hormone secretion, but also the secretion of several other hormones. The role of somatostatin in prolactin (PRL) secretion has not been clearly demonstrated. The present study was undertaken to examine the effects of somatostatin on rat PRL secretion in several different circumstances where the circulating PRL level is elevated: (1) the estradiol primed intact male rat, (2) normal and (3) estradiol primed rats pretreated with pimozide, (4) normal and (5) estradiol primed hypophysectomized male rats with adenohypophyses grafted under the kidney capsule (HAG rat). Blood samples (70 μL) were taken every 2 min via an indwelling atrial cannula from conscious, unrestrained animals. In the estradiol primed intact rats, a bolus injection of somatostatin (10, 100, and 1000 μg/kg) lowered PRL levels in a dose-dependent manner. When the PRL concentration was elevated by the administration of pimozide (3 mg/kg), a dopaminergic receptor blocking agent, somatostatin was ineffective in decreasing plasma PRL concentration but the PRL concentration was lowered by somatostatin when the rat had been primed with estradiol. Somatostatin had no effect on the normal HAG rats, but lowered the plasma PRL concentration in the estradiol primed HAG rats. Since somatostatin inhibits PRL secretion only in the estradiol primed rats, it is suggested that estradiol priming creates a new environment, presumably via new or altered receptors, which can be inhibited by somatostatin.


2004 ◽  
Vol 180 (1) ◽  
pp. 35-43 ◽  
Author(s):  
LA Nolan ◽  
CK Thomas ◽  
A Levy

The anterior pituitary is active mitotically and apoptotically under basal conditions and in response to a variety of physiological and pathophysiological stimuli. Hypothyroidism in man is associated with a modest but very occasionally dramatic increase in overall pituitary size. The mechanisms underlying this reversible phenomenon remain obscure. In the present study we have examined young adult rat anterior pituitary following surgical thyroidectomy and subsequent thyroid hormone treatment and withdrawal using an extremely accurate system for quantifying directly identified mitotic and apoptotic events. Despite the expected increase in the number and/or proportion of immunohistochemically identifiable thyrotrophs three weeks after thyroidectomy, mitotic and apoptotic activity remained unchanged, as did pituitary wet weight, in comparison with sham-operated and intact controls. In contrast, mitotic but not apoptotic activity was enhanced by treatment of thyroidectomized animals with thyroid hormones (triiodothyronine (T3) and thyroxine (T4) 1.8 microg and 3.6 microg/100 g body weight per day respectively), and once again declined to levels seen in intact animals within 72 h of subsequent thyroid hormone withdrawal. Thyroid hormone-induced enhancement of mitotic activity was also seen in intact rats treated with similar doses of thyroid hormones for 7 days and in thyroidectomized rats treated for a similar period with very low dose thyroid hormone replacement at a level that had no effect on raised hypothalamic TRH- or pituitary TSHbeta-transcript prevalence (0.018 microg T3 plus 0.036 microg T4/100 g body weight per day). Thus changes in mitotic and apoptotic activity are unlikely to be the principle mechanism for the apparent increase in thyrotrophs up to 4 weeks after thyroidectomy. In contrast, the data indicate that thyroid hormones have a permissive effect on anterior pituitary mitotic activity in thyroidectomized male rats. Thyroid hormone-induced enhancement of mitotic activity in intact rats further suggests that in euthyroid rats, ambient thyroid hormone levels are a limiting factor for anterior pituitary mitotic activity. In summary, this time course study of young, male rats has shown for the first time that thyroidectomy, thyroid hormone replacement and subsequent withdrawal has no significant effect on anterior pituitary apoptotic activity. Secondly, it has shown that the anterior pituitary mitotic response to thyroidectomy is blocked by complete thyroid hormone deprivation, but can be restored by very low level thyroid hormone replacement, and thirdly that in intact animals thyroid hormone levels significantly limit anterior pituitary mitotic activity.


1985 ◽  
Vol 249 (3) ◽  
pp. E276-E280 ◽  
Author(s):  
W. S. Evans ◽  
R. J. Krieg ◽  
E. R. Limber ◽  
D. L. Kaiser ◽  
M. O. Thorner

The effects of gender and the gonadal hormone environment on basal and stimulated growth hormone (GH) release by dispersed and continuously perifused rat anterior pituitary cells were examined. Cells from intact male and diestrus day 2 female rats and from castrate male rats either untreated or treated with testosterone (T) or 17 beta-estradiol (E2) were used. Basal GH release (ng/min per 10(7) cells; mean +/- SE) by cells from diestrus day 2 female rats was less than by cells from castrate rats treated with T (4.3 +/- 0.6 vs. 11.4 +/- 2.7, respectively; P less than 0.025). No other differences in basal release were detected. Concentration-response relationships were documented between human GH-releasing factor 40 (hGRF-40; 0.03-100 nM given as 2.5-min pulses every 27.5 min) and GH release. Mean (+/- SE) overall GH release (ng/min per 10(7) cells) above base line was greater by cells from intact male rats (496 +/- 92) than by cells from castrate (203 +/- 37.3; P less than 0.0001), castrate and T-treated (348 +/- 52.8; P = 0.008), or castrate and E2-treated (58.1 +/- 6.8; P less than 0.001) male rats or by diestrus day 2 rats (68.6 +/- 9.5; P = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)


1991 ◽  
Vol 261 (2) ◽  
pp. E227-E232 ◽  
Author(s):  
J. P. Schroder-van der Elst ◽  
D. van der Heide ◽  
J. Kohrle

In vitro, the synthetic flavonoid EMD 21388 appears to be a potent inhibitor of thyroxine (T4) 5'-deiodinase and diminishes binding of T4 to transthyretin. In this study, in vivo effects of long-term administration of EMD 21388 on thyroid hormone production and metabolism were investigated. Intact male rats received EMD 21388 (20 mumol.kg body wt-1.rat-1.day-1) for 14 days. [125I]T4 and 3,5,3'-[131I]triiodotyronine (T3) were infused continuously and intravenously in a double-isotope protocol for the last 10 and 7 days, respectively. EMD 21388 decreased plasma thyroid hormone concentrations, but thyrotropin levels in plasma and pituitary did not change. Plasma clearance rates for T4 and T3 increased. Thyroidal T4 secretion was diminished, but T3 secretion was elevated. Extrathyroidal T3 production by 5'-deiodination was lower. T4 concentrations were markedly lower in all tissues investigated. Total tissue T3 was lower in brown adipose tissue, brain, cerebellum, and pituitary, tissues that express the type II 5'-deiodinase isozyme due to decreased local T3 production. Most tissues showed increased tissue/plasma ratios for T4 and T3. These results indicate that this flavonoid diminished T4 and increased T3 secretion by the thyroid, probably in analogy with other natural flavonoids, by interference with one or several steps between iodide uptake, organification, and hormone synthesis.


1971 ◽  
Vol 51 (3) ◽  
pp. 473-481 ◽  
Author(s):  
H. M. LLOYD ◽  
J. D. MEARES ◽  
JOAN JACOBI ◽  
FRANCES J. THOMAS

SUMMARY A single 12 mg dose of stilboestrol dipropionate given to 100-day-old male rats resulted in increased pituitary mitotic activity, pituitary weight and serum growth hormone; the latter rose from a mean value of 20 ng/ml to a maximum of 342 ng/ml 9 days later. Serum growth hormone and pituitary mitotic activity then gradually diminished but were still slightly increased on day 28. Serum growth hormone and pituitary weight were significantly correlated during the periods of rapidly rising and of sustained high levels of serum growth hormone. Indices of mitotic activity were correlated with serum growth hormone during the periods of rapidly rising and of falling levels of serum growth hormone.


1973 ◽  
Vol 58 (2) ◽  
pp. 227-231 ◽  
Author(s):  
H. M. LLOYD ◽  
J. D. MEARES ◽  
JOAN JACOBI

SUMMARY The effects of a single injection of 1 mg diethylstilboestrol dipropionate on pituitary mitotic activity and on secretion of growth hormone and prolactin were investigated in male rats on each of the first 15 days following the single dose and then at intervals for a total period of 63 days. Mitotic activity increased to a maximum on day 4 and then gradually diminished. Serum growth hormone was moderately increased during the 2nd week and serum prolactin showed a gradual rise with a return to normal on day 63. In the pituitary gland, growth hormone concentration diminished until day 28, whereas prolactin rose quickly at first, maintained a raised level and increased further on day 43. During the first 12 days, pituitary weight was significantly correlated with serum growth hormone and prolactin concentration. During days 13–28, serum prolactin, but not growth hormone, was significantly correlated with the pituitary mitotic index.


2021 ◽  
Vol 53 (2) ◽  
Author(s):  
Amelya Permata Sari ◽  
Cimi Ilmiawati ◽  
Mohamad Reza

High-dose Monosodium Glutamate (MSG) expo sure increases the estrogen level in pregnant rats. However, there are limited data available on whether the MSG-related maternal hormonal effects can affect male litters' genitalia phenotype. This study aimed to analyze the impact of MSG on estrogen level in pregnant rats and anogenital distance in male pups. Experiment for this study was performed at the animal facility of Biomedical Laboratory at the Faculty of Medicine, Universitas Andalas, from April 2019 to February 2020. Pregnant Wistar rats were given MSG orally at 2 and 4 mg/g body weight (BW) for 20 days. On day 21, pregnant rats were sacrificed and blood was drawn intracardially. Estradiol serum level was measured by ELISA. Male pups were counted, and the anogenital distance (AGD) was measured. Maternal serum estradiol levels were statistically analyzed by One-Way ANOVA and the AGD of male litters were analyzed by the Kruskal-Wallis test. Results showed that perinatal MSG exposure increased the estradiol level (26.3±4.5 pg/ml; 37.5±6.7 pg/ml; 62.1±8.2 pg/ml in control, 2 mg/g BW, and 4 mg/g BW group, respectively [mean±SD; p=<0.001]) and decreased the AGD (4 mm; 3 mm; 1.5 mm in control, 2 mg/g BW, and 4 mg/gBW group, respectively [median; p=<0.01]) in a dose-dependent manner. Thus, MSG exposure during pregnancy is a risk factor for male rat feminization.


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.


2020 ◽  
Vol 10 ◽  
Author(s):  
Neveen Asmet Farag ◽  
Ayman S Mohamed ◽  
Hanan Farag El Sayed ◽  
Eman Y. Salah EL-Din ◽  
Abdel Rahman A. Tawfik

Background:: Infertility is the first-rate public health trouble affecting one in five married couples globally, male causes embody a significant proportion. Natural products could be an alternative or complementary inexpensive treatment for such matters. Echinochrome (Ech) is a natural quinone pigment obtained from sea urchin, and it was confirmed to possess many pharmacological properties due to its chemical activity. Objective:: The current research paper was targeted to evaluate the potential effects of Ech on male fertility, and to highlight the possible involved mechanisms. Methods:: Eighteen adult male rats were randomly distributed into three groups: control (1 ml of 2% DMSO, p.o.), low dose Ech (0.1 mg/kg, p.o.), and high dose Ech (1 mg/kg p.o.). Results:: The high dose Ech caused a significant decline in the levels of glucose, ALT, AST, ALP, urea, Cr, uric acid, TG, TC and LDL-C and testicular tissue MDA, while it caused a significant rise in the levels of albumin, TP, HDL-C, FSH, LH, testosterone and testicular tissue GSH activity. Moreover, it showed a significant positive effect on the testis weight, caudal epididymis weight, sperm count, sperm motility, sperm morphology, fructose concentration, and α-glucosidase activity. However, no significant changes were observed in histological examination of testicular tissue among all groups. Conclusion:: High dose Ech improved male rat-fertility either directly by activating the pituitary gonadal axis, and or indirectly via enhancing: the renal and hepatic functions, the lipid profile and or the antioxidant pathways.


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