Testicular and serum levels of inhibin and expression of inhibin subunit mRNAs are differentially affected by hemicastration in rats of various ages

1994 ◽  
Vol 141 (1) ◽  
pp. 143-151 ◽  
Author(s):  
I A Klaij ◽  
M A Timmerman ◽  
P Kramer ◽  
H M A Meijs-Roelofs ◽  
F H de Jong
Keyword(s):  
Mrna Expression ◽  
Serum Levels ◽  
Α Subunit ◽  
Post Translational Modifications ◽  
Subunit Mrna ◽  
Age Related ◽  
Testicular Weight ◽  
Mrna Content ◽  
Old Rats

Abstract Age-related short-term effects of hemicastration on testicular weight, serum FSH, immunoreactive inhibin, LH and testosterone, testicular levels of inhibin subunit mRNA expression, and bioactive and immunoreactive inhibin were studied in rats of 8, 15 and 22 days of age. Hemicastration led to an increased weight of the remaining testis after 24 h in 8- and 15-day-old rats, but not in 22-day-old rats. Serum FSH levels were elevated in all hemicastrated rats after 8 h. However, serum immunoreactive inhibin levels were decreased only after 72 h in 8-day-old rats and after 24 h in 15- and 22-day-old rats. Inhibin α-subunit mRNA expression was increased in the testes of hemicastrated rats of 8 and 15 days of age, whereas inhibin βB-subunit mRNA expression was elevated in the testes of 15-day-old rats but not in those of 8- and 22-day-old rats. The increase in α-subunit mRNA content per testis was caused by an increased concentration and increased testicular weight, whereas the increase in βB-subunit mRNA in the remaining testis parallelled the increased testicular weight, indicating that different mechanisms play a role in the regulation of these mRNAs. In 22-day-old rats, a transiently decreased expression of inhibin βB-subunit mRNA was observed 8 h after hemicastration. The increased inhibin α- and βB-subunit mRNA expression in 8- and 15-day-old rats did not result in increased testicular bioactive and immunoreactive inhibin content of the remaining testis, whereas in 22-dayold rats an increased immunoreactive inhibin content of the remaining testis was observed. These data indicate that efficiency of translation, post-translational modifications or transport from the testis play an important role in determining the final testicular content of inhibin. In conclusion, the response of the remaining testis and the role of inhibin in the regulation of the pituitary-testis axis after unilateral castration depend on the age at which the animals are hemiorchidectomized. Journal of Endocrinology (1994) 141, 143–151

Effects of FSH and testosterone on highly purified rat Sertoli cells: inhibin α-subunit mRNA expression and inhibin secretion are enhanced by FSH but not by testosterone

1989 ◽  
Vol 122 (3) ◽  
pp. 757-762 ◽  
Author(s):  
A. M. W. Toebosch ◽  
D. M. Robertson ◽  
I. A. Klaij ◽  
F. H. de Jong ◽  
J. A. Grootegoed
Keyword(s):  
Mrna Expression ◽  
Effective Dose ◽  
Sertoli Cell ◽  
Germ Cells ◽  
Sertoli Cells ◽  
Osmotic Shock ◽  
Shock Treatment ◽  
Α Subunit ◽  
Subunit Mrna ◽  
Old Rats

ABSTRACT The effects of FSH and testosterone on inhibin mRNA expression and inhibin production by highly purified Sertoli cell preparations were examined. Sertoli cells were isolated from testes of 22-day-old rats by sequential trypsin, collagenase and hyaluronidase treatments, with subsequent osmotic shock treatment on day 3 of culture. Contamination by peritubular and germ cells was <0·5 and 1–3% respectively. Intracellular and secreted inhibin levels were measured by radioimmunoassay, using Sertoli cells which were incubated for 24 h in the absence or presence of FSH and testosterone from days 4 to 5 of culture. FSH stimulated the cellular inhibin content and the secreted inhibin level by four- and sevenfold respectively, with a half-maximal effective dose of 5–50 ng/ml. Under the present incubation conditions, testosterone (1 μmol/l) had no effect on immunoreactive inhibin levels in either the presence or absence of FSH. Similarly, the expression of inhibin α-subunit mRNA was increased following FSH stimulation, whereas testosterone had no effect. The expression of inhibin βB-subunit mRNAs was not influenced by FSH or testosterone. It is concluded that highly purified Sertoli cell preparations, with a very low number of peritubular or germ cells, are fully responsive to FSH with respect to inhibin mRNA expression and inhibin production. Journal of Endocrinology (1989) 122, 757–762

Age-related discrepancies between serum and pituitary gonadotrophin, and pituitary gonadotrophin subunit mRNA responses to castration and testosterone replacement in male rats

1992 ◽  
Vol 135 (3) ◽  
pp. 507-515 ◽  
Author(s):  
P. Pakarinen ◽  
I. Huhtaniemi
Keyword(s):  
Serum Levels ◽  
Male Rats ◽  
Testosterone Replacement ◽  
Translation Efficiency ◽  
Mrna Levels ◽  
Α Subunit ◽  
Subunit Mrna ◽  
Age Related ◽  
Serum Lh ◽  
Good Agreement

ABSTRACT The responses of gonadotrophin gene expression, pituitary content and serum levels to castration alone and castration plus testosterone replacement (silicone elastomer implants) were compared in male rats at 10, 30, 60 and 90 days of age. Sham-operated animals served as controls. In addition, 30-day-old castrated rats were treated with dihydrotestosterone (DHT) and diethylstilboestrol (DES). When killed 7 days after castration, the increases in serum LH (six- to eightfold; P < 0·01) and FSH (two- to fourfold; P < 0·01) were similar at all ages studied. Likewise, testosterone reversed the effects of castration in a largely similar fashion at all ages. In contrast, great age-related differences were observed in the responses of gonadotrophin subunit mRNAs to the treatments. Castration increased the common α subunit mRNA two- to fourfold on days 10 and 30 (P < 0·01), sixfold on day 60 (P < 0·01), but not at all on day 90. Testosterone reversed the increases at all ages, but the levels were below those of controls only at 90 days (P < 0·01). The highest increases (sixfold; P < 0·01) of LH-β mRNA were seen on days 10 and 60, the others being two- to threefold higher (P < 0·05–0·01). Testosterone reversed this effect at 60 days and suppressed LH-β mRNA to below the control levels at other ages (P < 0·01). Castration had no effect on FSH-β subunit mRNA at 30 and 90 days but a four-to fivefold increase was seen on days 10 and 60 (P < 0·01). Testosterone suppressed these mRNAs at all ages, and they decreased to below the levels in controls at 30 and 60 days. Testosterone, DHT and DES had, at 30 days, practically the same effects on the LH parameters, whereas DHT was clearly less effective than testosterone and DES in suppressing those of FSH. In conclusion, although there was, in general, good agreement between gonadotrophin mRNA and serum levels in response to castration and testosterone replacement, there were specific ages when the post-castration increases in FSH and/or LH occurred with no detectable change in the respective mRNA levels. These findings indicate that altered transcription (or mRNA stability) is not solely responsible for the responses of the gonadotrophins to altered gonadal feedback, but that changes in translation efficiency and/or serum gonadotrophin stability are involved at specific ages of development. Journal of Endocrinology (1992) 135, 507–515

An age-related difference in hyperoxia lethality: role of lung antioxidant defense mechanisms

1995 ◽  
Vol 268 (4) ◽  
pp. L539-L545 ◽  
Author(s):  
A. T. Canada ◽  
L. A. Herman ◽  
S. L. Young
Keyword(s):  
Defense Mechanisms ◽  
Antioxidant Defense ◽  
Fischer 344 Rats ◽  
Fischer 344 ◽  
Related Difference ◽  
Age Related ◽  
65 H ◽  
Old Rats ◽  
Gpx Activity

The role of animal age in the lethal response to > 98% oxygen has been extensively studied, with the observation that neonatal rats were resistant while mature animals were sensitive. Antioxidant enzymes increased during the oxygen exposure in neonatal but not in mature rats, suggesting they were important in the age-related toxicity difference. Because no studies had compared the response of mature and old rats to hyperoxia, we exposed Fischer 344 rats, aged 2 and 27 mo, to > 98% oxygen. Unexpectedly, the old rats lived significantly longer than young, 114 and 65 h, respectively. No histopathological differences were found to explain the results. Of the antioxidants, only glutathione peroxidase (GPx) activity was higher in the lungs of nonexposed old rats. Superoxide dismutase (SOD) was higher in the young, results opposite those expected if SOD was important in the lethality difference. No antioxidant induction occurred in the old oxygen-exposed rats. These results suggest that although there may be a role for GPx, mechanisms in addition to antioxidant protection and inflammation are likely responsible for the age-related difference in hyperoxia lethality.

scholarly journals Temporal and hormonal regulation of inhibin protein and subunit mRNA expression by post-natal and immature rat ovaries

2000 ◽  
Vol 166 (2) ◽  
pp. 339-354 ◽  
Author(s):  
AE Drummond ◽  
M Dyson ◽  
E Thean ◽  
NP Groome ◽  
DM Robertson ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Cell Cultures ◽  
Granulosa Cells ◽  
Inhibin B ◽  
Alpha Subunit ◽  
Inhibin A ◽  
Preantral Follicles ◽  
Subunit Mrna ◽  
Ovarian Cells ◽  
Old Rats

The contribution of specific follicle populations to dimeric inhibin production and inhibin subunit mRNA expression by the rat ovary has been investigated in two model systems, granulosa cells isolated from 25-day-old diethylstilboestrol (DES)-treated rats and post-natal rat ovaries, dispersed in culture or whole ovaries, using specific two-site immunoassays and 'real time' PCR. Media from FSH-stimulated granulosa cell cultures fractionated by gel filtration and RP-high performance liquid chromatography revealed two predominant peaks of alpha subunit activity which were attributed to alpha subunit and 31 k dimeric inhibin-A. The corresponding inhibin-B levels were low. FSH stimulation did not alter the ratio of inhibin-A:alpha subunit produced by granulosa cells. All three inhibin subunit mRNAs were expressed by granulosa cells, with eight-fold more alpha subunit mRNA relative to either of the beta subunits. Administration of DES to immature rats prior to the isolation of granulosa cells from the ovary led to beta(A) and beta(B) mRNA expression being down-regulated in the absence of any significant change in alpha subunit expression by the granulosa cells. Inhibin-A, -B and -alpha subunit were produced by basal and stimulated cultures of ovarian cells prepared from 4-, 8- and 12-day-old rats, indicating that primary, preantral and antral follicles contribute to total inhibin production. Consistent with these results, follicles within these ovaries expressed all three inhibin subunit mRNAs, with maximal expression observed in the ovaries of 8-day-old rats. The appearance of antral follicles in the ovary at day 12 led to a decline in the mRNA levels of each of the subunits but was most evident for the beta subunits. There was a profound influence of secondary preantral follicles on dimeric inhibin-A production, with FSH stimulation increasing inhibin-A relative to alpha subunit levels in cultures of ovarian cells prepared from 8-day-old rats. Thus, preantral follicles exposed to FSH contribute significantly to beta(A) subunit production by the ovary. In contrast, primary and preantral follicles did not produce inhibin-B in response to FSH stimulation. Transforming growth factor-beta (TGF-beta) enhanced, in a time-dependent manner, the production of the inhibin forms by ovarian cells in culture, although inhibin-B production was not responsive until day 8. The simultaneous treatment of ovarian cell cultures with FSH and TGF-beta elicited the greatest increases in production of all the inhibin forms. In summary, ovaries of 4-, 8- and 12-day-old rats expressed inhibin subunit mRNAs and produced dimeric inhibin-A and -B and free alpha subunit. Preantral follicles (day-8 ovarian cell cultures) were particularly sensitive to stimulation by FSH and TGF-beta and had a substantial capacity for inhibin production. The production of oestrogen by follicles may be instrumental in regulating inhibin production given that beta subunit mRNA expression was down-regulated by DES. The mechanisms by which inhibin-A and inhibin-B are individually regulated are likely to be similar during the post-natal period, when folliculogenesis is being established, and diverge thereafter, when inhibin-A becomes the predominant form in the fully differentiated ovary.

scholarly journals Increased Frequency of Circulating Follicular Helper T Cells in Children with Hand, Foot, and Mouth Disease Caused by Enterovirus 71 Infection

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Jianping Wu ◽  
David Cui ◽  
Xianzhi Yang ◽  
Jianzhou Lou ◽  
Jie Lin ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Enterovirus 71 ◽  
Foot And Mouth Disease ◽  
Serum Levels ◽  
Mouth Disease ◽  
Ev71 Infection ◽  
Tfh Cells ◽  
Follicular Helper ◽  
Foot And Mouth

Enterovirus 71 (EV71) is a major causative agent of hand, foot, and mouth disease (HFMD) in children. The role of T follicular helper (TFH) cells in EV71-infected children remains unclear in regulating humoral immunity. The frequency of circulating ICOShigh/PD-1highCXCR5+CD4+TFH cells in the children with mild and severe EV71 infection and healthy controls (HC) was detected by flow cytometry, respectively. IL-21 and IL-6 mRNA expression and their serum levels, Bcl-6 mRNA expression, and specific neutralizing antibodies against EV71 (NAb-EV71) were measured. In the acute stage of patients with EV71 infection, increased frequencies of circulating TFH cells with ICOShighand PD-1highexpression in the mild and severe patients were observed, and the positive correlations among the frequencies of circulating TFH cells and the serum levels of IL-21, IL-6, and NAb-EV71 titres were detected, respectively. Moreover, the expressions of IL-6 and IL-21 mRNA in PBMCs from patients were also significantly higher than those of HC. However, further analysis did not reveal any significant differences between mild and severe patients. These data indicate a role of TFH cells and associated cytokines in modulating the humoral response during the pathogenesis of EV71 infection.

scholarly journals Alpha-Synuclein Post-translational Modifications: Implications for Pathogenesis of Lewy Body Disorders

2021 ◽  
Vol 13 ◽  
Author(s):  
Nelson de Oliveira Manzanza ◽  
Lucia Sedlackova ◽  
Raj N. Kalaria
Keyword(s):  
Neurodegenerative Diseases ◽  
Lewy Body ◽  
Clinical Symptoms ◽  
Lewy Bodies ◽  
Alpha Synuclein ◽  
Lewy Neurites ◽  
Post Translational Modifications ◽  
Age Related ◽  
Neurodegenerative Dementias

Lewy Body Disorders (LBDs) lie within the spectrum of age-related neurodegenerative diseases now frequently categorized as the synucleinopathies. LBDs are considered to be among the second most common form of neurodegenerative dementias after Alzheimer's disease. They are progressive conditions with variable clinical symptoms embodied within specific cognitive and behavioral disorders. There are currently no effective treatments for LBDs. LBDs are histopathologically characterized by the presence of abnormal neuronal inclusions commonly known as Lewy Bodies (LBs) and extracellular Lewy Neurites (LNs). The inclusions predominantly comprise aggregates of alpha-synuclein (aSyn). It has been proposed that post-translational modifications (PTMs) such as aSyn phosphorylation, ubiquitination SUMOylation, Nitration, o-GlcNacylation, and Truncation play important roles in the formation of toxic forms of the protein, which consequently facilitates the formation of these inclusions. This review focuses on the role of different PTMs in aSyn in the pathogenesis of LBDs. We highlight how these PTMs interact with aSyn to promote misfolding and aggregation and interplay with cell membranes leading to the potential functional and pathogenic consequences detected so far, and their involvement in the development of LBDs.

scholarly journals Modulatory effects of PKC activity on increased 92-kDa gelatinase secretion by neonatal alveolar macrophages

1997 ◽  
Vol 273 (5) ◽  
pp. L989-L996 ◽  
Author(s):  
Christophe Delacourt ◽  
Patricia Rouet-Benzineb ◽  
Christophe Delclaux ◽  
Jeannique L’Hour ◽  
Alain Harf ◽  
...  
Keyword(s):  
Alveolar Macrophages ◽  
Postnatal Period ◽  
Calpain Inhibitor ◽  
Calpain Activity ◽  
Adult Rats ◽  
Age Related ◽  
Key Factor ◽  
Old Rats ◽  
High Level

We previously demonstrated that alveolar macrophages (AMs) from neonatal rats can secrete more 92-kDa gelatinase than AMs from adult rats. In this study, we investigated the role of the protein kinase C (PKC) pathway in the transductional regulation of 92-kDa gelatinase secretion by rat AMs, and we also evaluated maturational changes in this role with increasing postnatal age. After AM stimulation by phorbol 12-myristate 13-acetate (PMA), we observed a dose-dependent increase in gelatinase secretion that was significantly more marked in AMs from 6-day-old rats than in AMs from adult rats and that was inhibited by the PKC inhibitor calphostin C. Adenosine 3′,5′-cyclic monophosphate mimetics or concanavalin A failed to induce an increase in gelatinase secretion by AMs. Time-dependent variations in PKC activity after PMA stimulation differed significantly between 6-day-old rats and adult rats; PKC activity decreased in adult AMs (50%) but remained stable in 6-day-old AMs. We therefore investigated age-related differences in the intracellular proteolytic degradation of PKC, which is thought to be mediated by calpains. Leupeptin, used as a calpain inhibitor, inhibited the decrease in PKC activity after exposure of adult AMs to PMA and induced a greater than threefold increase in PMA-induced gelatinase secretion. Calpain activity was significantly lower in AM extracts from 6-day-old than from adult rats. The physiological implication of these developmental changes in 92-kDa gelatinase regulation was demonstrated by investigation of AMs from 1-day-old rats that showed a high level of spontaneous PKC-dependent gelatinase secretion coexisting with very low calpain activity. We conclude that sustained PKC activity is a key factor in the increased gelatinase secretion by AMs seen during the postnatal period and is due, at least in part, to reduced PKC degradation.

IGFBP mRNA expression in small intestine of rat during postnatal development

2001 ◽  
Vol 281 (6) ◽  
pp. G1378-G1384 ◽  
Author(s):  
C. A. Shoubridge ◽  
C.-B. Steeb ◽  
L. C. Read
Keyword(s):  
Mrna Expression ◽  
Postnatal Development ◽  
Age Groups ◽  
Rat Intestine ◽  
Age Related ◽  
Igf I ◽  
Igf Binding ◽  
Old Rats ◽  
Igf Binding Protein ◽  
Igfbp 3

In contrast to the adult gut, the immature intestine is refractory to subcutaneously infused insulin-like growth factor I (IGF-I). IGF binding protein (IGFBP) mRNA expression was characterized in intestinal tissues from 6-, 19-, and 90-day-old rats to determine if changes in local expression could account for this age-related change in IGF-I potency. For all age groups, IGFBP-3 to -6, but not IGFBP-1 or -2, were detected by Northern blot analysis. IGFBP-3, -4, and -5 were more intensely expressed in the 6-day-old rat intestine compared with weanling or adult tissue. In contrast, IGFBP-6 expression peaked at the time of weaning. In situ hybridization showed IGFBP-3 to -6 expression was confined to cells of the lamina propria and submucosa and also in the muscularis layer for IGFBP-5. Furthermore, the pattern of IGFBP-5 localization in the intestine changed with development. The findings indicate that the expression of IGFBP-3 to -6 is higher in the immature intestine compared with the adult intestine, suggesting locally produced IGFBPs may inhibit systemically derived IGF-I action in the intestine. Therefore, changes to local IGFBP expression may contribute to the varying response of the rat intestine to IGF-I peptides during postnatal development.

Old Rats Are More Susceptible to Induction of Benign Prostatic Hyperplasia (BPH) at Comparative to Young Mature

2021 ◽  
Vol 14 ◽  
Author(s):  
Vladimir G. Bespalov ◽  
Valerij A. Alexandrov ◽  
Alexander L. Semenov ◽  
Grigory V. Tochilnikov ◽  
Elena D. Ermakova ◽  
...  
Keyword(s):  
Metabolic Disorders ◽  
Serum Testosterone ◽  
The Body ◽  
Prostate Hyperplasia ◽  
Age Related ◽  
Low Concentrations ◽  
Male Wistar Rats ◽  
Old Rats ◽  
Intact Rats

Aims: The aim of the experiments was to find out the factors on which age-related sensitivity to the occurrence of BPH depends. Methods: 45 male Wistar rats aged 3 and 24 months were used. In each age group there were intact rats and animals with induced BPH (by surgical castration + testosterone injections, 25 mg/kg x 7). On the 36th day of the experiment, blood was taken from rats to determine serum testosterone, cholesterol, triglycerides and glucose; then the animals were autopsied, their prostates were weighed, and their morphology was studied. Results: Young mature intact rats had much higher testosterone levels (6.2±0.93 nmol/l) than old intact (3.8±0.55 nmol/l), while the ratio of prostate weight was inverse. The weight of the prostate and prostatic index in old rats with induced BPH was significantly higher not only in comparison with the old intact rats but also with young animals after BPH induction. Morphologically, the inflammatory foci were determined not only in the prostates of old rats, which induced BPH, but also in intact animals. Besides in old intact rats, the foci of prostate hyperplasia were often noted. Conclusions: Our experimental model indicates the important role of non-bacterial prostatitis in the pathogenesis of BPH. No metabolic disorders in BPH induction were revealed. The sensitivity of the prostate of old rats to BPH development is increasing despite the low concentrations of testosterone in the body. Age sensitivity to BPH is probably determined by a higher expression of androgen receptors in old animals.

Sign in / Sign up

Export Citation Format

Share Document