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Biomedical subjects

I Huhtaniemi

Publications and source records attributed to I Huhtaniemi.

At least 91 records · Page 5Linked to original sources
PubMed1998

Recombinant forms of rat and human luteinizing hormone and follicle-stimulating hormone; comparison of functions in vitro and in vivo.

We have previously described the preparation, purification and partial characterization of recombinant (rec) forms of rat luteinizing hormone (LH) and follicle-stimulating hormone (FSH). In the present study, the special functional features of these hormones were studied further, in vitro and in vivo, and compared with human recLH and recFSH, as well as with human urinary choriongonadotropin (hCG) and rat pituitary LH (NIDDK-RP3). In radioreceptor assay, the affinity of hCG binding to rat testis membranes was 5-fold higher than that of human recLH and 100-fold higher than that of rat recLH. In in vitro bioassay, using dispersed adult mouse interstitial cells or a mouse Leydig tumor cell line (BLT-1), hCG and human recLH were 10- to 20-fold more potent than rat recLH. Correspondingly, rat pituitary LH was about 10-fold less potent than rat recLH, and evoked a maximum testosterone response that was about half of that elicited by the other LH/CG preparations. Rat recFSH was about 10-fold less potent than human recFSH in stimulating cAMP production of a mouse Sertoli cell line (MSC-1) expressing the recombinant rat FSH receptor. The circulating half-times (T1/2) of rat and human rec hormones were assessed after i.v. injections into adult male rats rendered gonadotropin-deficient by treatment with a gonadotropin-releasing hormone antagonist. A novel immunometric assay was used for the rat FSH measurements. In the one-component model the T1/2 values of rat and human recLH were 18.2 +/- 1.9 min (n = 7) and 44.6 +/- 3.1 min (n = 7) respectively and those of rat and human recFSH were 88.4 +/- 10.7 min (n = 6) and 55.0 +/- 4.2 min (n = 6) respectively; the two-component models revealed similar differences between the rec hormone preparations. Collectively, rat recLH was eliminated significantly faster from the circulation than human recLH (P < 0.0001). In contrast, the elimination of rat recFSH was significantly slower than that of human recFSH (P = 0.02). In conclusion, rat recFSH and rat recLH display lower biopotencies per unit mass than the respective human hormones in vitro, and also in vivo for LH. This is paralleled by shorter T1/2 of rat recLH than the respective human hormone in the circulation, whereas human recFSH has a shorter T1/2 than human FSH. The special functional features of the rat rec gonadotropins emphasize the use of these preparations on studies of gonadotropin function in the rat, an important animal model for reproductive physiology.

Animals↗
PubMed1997

The mouse relaxin-like factor gene and its promoter are located within the 3' region of the JAK3 genomic sequence.

Isolation and sequencing of a genomic clone encoding the mouse gene for the relaxin-like factor (RLF), which is endogenously expressed to a high level exclusively in Leydig cells, indicated that similar sequences were also present at the 3' end of the mouse JAK3 gene, a gene expressed predominantly in lymphoid tissues. More extensive Southern blot, polymerase chain reaction and sequencing analyses showed that the published mouse sequence for exon 23 of the JAK3 gene in fact comprises two exons, 23A and 23B, separated by an additional novel intron of 2.2 kb, and that within this intron the promoter and exon 1 of the mouse RLF gene are encoded. The two overlapping transcripts appear to use different polyadenylation signals in the common 3' untranslated region of exon 23B. Transient transfection of different RLF promoter reporter constructs into Leydig, Sertoli, granulosa and kidney cell lines indicate that as little as 0.7 kb of the region upstream of exon 1 of the RLF gene, and within the novel intron 22 of the JAK3 gene, is sufficient to account for cell-specific expression of the RLF gene. This promoter region is specifically hypomethylated in Leydig cells compared to non-expressing tissues.

Animals↗
PubMed1997

Involvement of chloride channels in progesterone production during meiotic maturation of follicle-enclosed oocytes of Rana temporaria and Xenopus laevis.

The chloride channel blockers SITS (4-acetamido-4'-isothiocyanostibene-2,2'-disulphonic acid) and DIDS (4,4'-diisothiocyanostilbene-2,2'-disulphonic acid) markedly suppressed progesterone production in the Rana temporaria and Xenopus laevis follicle-enclosed oocytes and oocyte maturation stimulated by the homologous pituitary suspension and hCG, respectively. Inhibition was dose-dependent and decreased with the increase of the hormone concentration. SITS did not affect progesterone production in the R. temporaria follicle-enclosed oocytes stimulated by dbcAMP. Substitution of sodium chloride for equimolar concentrations of sodium gluconate, methanesulfonate, glutamate, or formate significantly potentiated the gonadotropin-stimulated progesterone production and oocyte maturation in the both species. Possible involvement of chloride channels in progesterone production by the gonadotropin-stimulated amphibian follicle-enclosed oocytes is discussed.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1997

Novel cationic liposomes for DNA-transfection with high efficiency and low toxicity.

Liposomes containing the natural cationic amphiphile, sphingosine and some of its derivatives were used for transfection of DNA in vitro. Multilamellar liposomes comprised of dioleoylphosphatidylethanolamine (DOPE), different sphingosine derivatives, and diacylglycerols with varying fatty acid chains, preincubated with DNA, transfected efficiently the KK-1 murine granulosa cells. Most efficient transfection on this cell line was achieved with liposomes composed of phytosphingosine, DOPE, and dioctanoylglycerol (DC8G) (64:31:4.8, molar stoichiometry), which gave expression of the transfected gene 2-10-fold higher than the commercial reagent Lipofectin. At higher doses the new liposomes also caused markedly less cell death of KK-1 cells. On COS-7 cells these liposomes showed slightly, but significantly lower transfection, of approximately 70%, of that gained with Lipofectin. The murine Sertoli cells, MSC-1, selectively resisted transfection by the sphingosine derivative based liposomes tested, giving only 11-14% of the expression detected in Lipofectin transfected cells of the same line. In conclusion, the novel liposomes formulated offer an effective, technically easy and economical method of transfection for a variety of cultured cell lines.

Animals↗
PubMed1997

Recombinant rat luteinizing hormone; production by Chinese hamster ovary cells, purification and functional characterization.

Rat recombinant (rec) luteinizing hormone (LH) was produced in Chinese hamster ovary (CHO) cells, to enable studies on LH physiology in this species with homologous hormone. The synthesized hormone was purified, and characterized physico-chemically and biologically in comparison with highly purified preparations of rat pituitary (pit) LH (NIDDK-rLH-I-7 and I-9) and to highly purified urinary (NIH, CR-121) and rec forms of human chorionic gonadotropin (hCG). The 33 kD molecular mass of rat recLH, as determined by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot, was comparable with the 32 kD size of pitLH. In chromatofocusing, the isoforms of rat recLH distributed in the pI range 6.5-7.8, similar to rat pitLH. In receptor binding assays using rat testicular membranes, and physiologic salt concentration, rat recLH displayed a 5-10-fold higher affinity than rat pitLH, but about 100-fold lower affinity than hCG. In contrast, in low salt concentrations the affinities of rat recLH and rechCG to rat LH receptor were rather similar. The differences in potency in the mouse Leydig cell in vitro bioassay were in agreement with the receptor binding data at physiologic salt concentration. Neither rat recLH nor pitLH stimulated cAMP production or bound specifically to HEK 293 cells expressing the rec human LH receptor. When injected subcutaneously on four consecutive days to male rats (8.4-33.7 microg/rat/day) rat recLH did not induce seminal vesicle growth in comparison with a significant effect of human menopausal gonadotropin (hMG; 12.5-50 IU/rat/day). In contrast, ovulation was induced in 5/6 and 6/6 female rats following single injections of 3.75 and 7.5 microg of rat recLH, respectively, after pretreatment with 10 microg/kg of a GnRH-antagonist (Org 30850). In conclusion, rat recLH displays clearly lower in vivo and in vitro bioactivity than hCG. Nevertheless, it binds effectively to the rat LH receptor (with affinity dependent on salt concentration) and is bioactive in the mouse Leydig cell bioassay. This newly synthesized recombinant hormone provides a useful tool for further studies on the physiology of LH action in the rat, the most common animal model in reproduction research.

Animals↗
PubMed1997

Recombinant rat follicle-stimulating hormone; production by Chinese hamster ovary cells, purification and functional characterization.

In order to obtain homologous follicle-stimulating hormone (FSH) for in vivo and in vitro studies in the rat, rat recombinant (rec) FSH was produced in Chinese Hamster Ovary (CHO) cells. The synthesized rat recFSH was purified and subjected to physico-chemical and biological characterization. including a comparison with two rat pituitary (pit) and reference preparations (NIDDK-rFSH I-8 and NIDDK-rFSH-RP2) as well as with human recFSH (Org 32489). The molecular masses of rat recFSH and human recFSH were determined by SDS-polyacrylamide (SDS-PAGE) and were found to be similar, about 40 kD. The pI distribution of rat recFSH is similar to rat pitFSH, and slightly more acidic than human recFSH (3.6-5.6 vs 3.9-5.5, respectively) as determined by isoelectric focussing in immobilized pH gradients. Rat recFSH displayed dose-response curves parallel and in the same dose range as the rat pitFSH in receptor binding and in vitro bioassays. However, the in vivo activities of rat recFSH and rat pitFSH were 8824 and 3051 IU/mg, respectively, determined by the Steelman Pohley assay. Rat (pit and rec) and human FSH are very different. Human recFSH bound to both calf testicular membranes and CHO cells expressing the human FSH receptor (CHO hFSH-R) with about 10-fold higher affinity (Ka) than pituitary and recombinant rat FSH. In in vitro bioassays with immature rat Sertoli cells and CHO hFSH-R cells human recFSH was also about 10-fold more potent than the rat FSH preparations. In the in vitro bioassays with immature rat granulosa cells the difference was about 5-10-fold. These studies indicate that the receptor binding and in vitro activities of rat pitFSH and rat recFSH are similar. The differences in in vivo activity are probably due to the differences in glycosylation. The biological behaviour of rat FSH (pit and rec) is different from that of human FSH. Therefore, if the rat is used as a model for physiology of gonadotropic action, the results may be greatly influenced by the type (species) of hormone preparation used. The availability of homologous hormone preparations is therefore crucial.

Animals↗
PubMed1997

Suppression of gonadotropins inhibits gonadal tumorigenesis in mice transgenic for the mouse inhibin alpha-subunit promoter/simian virus 40 T-antigen fusion gene.

We have previously developed a transgenic (TG) mouse model expressing the Simian virus 40 T-antigen (Tag), driven by a 6-kb fragment of the mouse inhibin alpha-subunit promoter (inh-alpha). The mice develop metastasizing gonadal tumors, of granulosa/theca or Leydig cell origin, with 100% penetrance by the age of 5-8 months. In the present study, we examined whether the appearance and growth of the gonadal tumors are dependent on gonadotropins. Gonadotropin suppression was achieved either by treatment of 3-month-old mice for 2-3 months with a GnRH antagonist (Cetrorelix, SB-75), or by cross-breeding the TG mice to the genetic background of the gonadotropin-deficient hypogonadal mutant mouse (hpg). Gonadal tumor growth was clearly inhibited by SB-75 treatment in one of the TG mouse lines (IT6-M), as indicated by the absence of macroscopically visible tumors and by reduced gonadal weights. Despite the suppressed gonadotropin secretion and Tag expression, hyperplasia of testicular Leydig, and ovarian stromal cells persisted in some of the treated mice. In another TG mouse line (IT6-F), with more aggressive tumorigenesis, the SB-75 treatment only partially inhibited gonadal tumor growth. None of the hypogonadotropic TG mice, homozygous for the hpg mutation, developed gonadal tumors. Their gonadal histology was indistinguishable from that of the non-TG hpg mice, suggesting total inhibition of gonadal tumorigenesis in the absence of gonadotropin stimulation. Tag expression and Leydig cell hyperplasia were apparent already in the postnatal TG mice but absent in those TG mice homozygous for the hpg mutation. In conclusion, the present results indicate that the gonadal tumorigenesis in our TG mouse model starts in early age as hyperplasia in specific somatic cells. Both this, and the subsequent malignant tumor growth, are gonadotropin dependent. A sufficient level of Tag expression, a prerequisite for gonadal tumorigenesis, only occurs upon gonadotropin stimulation.

Animals↗
PubMed1996

Lack of endogenous adenosine receptor activation explains the insensitivity of neonatal rat Leydig cells to treatment with pertussis toxin.

We have previously shown that the Gi protein-mediated negative modulation of FSH-stimulated cAMP production in neonatal rat Sertoli cells can be blocked by pretreatment with pertussis toxin (PT), an inhibitor of the Gi protein function. In contrast, hCG-stimulated testosterone (T) production by neonatal Leydig cells was insensitive to PT action, despite the demonstration of Gi protein in these cells by immunohistochemistry. We now tested the hypothesis that the missing Gi protein function in neonatal Leydig cells is due to absence of its endogenous activator, adenosine. It was first reconfirmed in dispersed cells of 7-day-old rats that PT preincubation enhanced FSH-stimulated cAMP production (i.e. Sertoli cell function), but had no effect on hCG-stimulated T production (Leydig cell function). The adenosine agonist n-phenylisopropyladenosine (PIA 1 mumol/l), acting through the Gi-protein, attenuated FSH-stimulated cAMP production, and this effect was abolished when the Gi protein was inactivated by preincubation with PT. PIA (1 mumol/l) also inhibited (P < 0.05-0.01) the basal and hCG-stimulated rates of Leydig cell T production, and the PIA effect was abolished by PT preincubation. In conclusion, the present data show that the apparent absence of a functional Gi protein function of neonatal Leydig cells is due to insufficient endogenous levels of the stimulating ligand, adenosine. When the Gi protein function is activated by exogenous adenosine agonist (PIA), the enhancement of hCG-stimulated T production by PT can be demonstrated. At the same time, the endogenous level of adenosine is sufficient for activation of the Gi protein function in Sertoli cells.

Animals↗
PubMed1996

The mouse inhibin alpha-subunit promoter directs SV40 T-antigen to Leydig cells in transgenic mice.

Testicular tumorigenesis was observed in transgenic mice expressing the 6-kb mouse inhibin alpha-subunit promoter/Simian virus 40 T-antigen (SV40 Tag) fusion gene. The tumors were confined to Leydig cells using immunohistochemistry with anti-Tag antibody, specific binding of biotinylated hCG and histochemistry for 3 beta-hydroxysteroid dehydrogenase. Leydig cell hyperplasia and presence of Tag protein in the testicular interstitial tissue were already evident at 5 and 6.5 days of age, respectively. An immortalized cell line, BLT-1, was established from one testicular tumor. These cells expressed the LH receptor and P450scc mRNAs, and displayed LH-responsive cAMP and progesterone production, and low testosterone production. The cells also specifically bound 125I-labeled recombinant human LH with high affinity (36000 binding sites/cell), and the binding was regulated by 8Br-cAMP and hCG. This gonadal tumor model is valuable for further studies on endocrine functions of Leydig cells and their tumorigenesis in vivo and in vitro.

3-Hydroxysteroid Dehydrogenases↗
PubMed1996

Regulation of function of the murine luteinizing hormone receptor promoter by cis- and trans-acting elements in mouse Leydig tumor cells.

The transcriptional activity of various lengths of the 5'-untranslated region (UTR) of the murine LH receptor (R) gene were studied using the luciferase reporter gene in transiently transfected mouse Leydig tumor cells (mLTC-1). Chinese hamster ovarian (CHO) and HeLa cells were used as controls. The basal transcriptional promoter activity in mLTC-1 cells resided within the first 173 base pairs (bp) of the 5'-UTR. Placing an LHR promoter fragment (bases -715/ -56) in front of the Herpes simplex virus thymidine kinase (TK) minimal promoter resulted in a 7-fold increase in luciferase activity. Deletion of bases -56 to -173 of the above construct totally abolished the increased luciferase activity, brought about by the LHR promoter sequences. Basically similar results on LHR promoter function were observed using CHO cells. In contrast, no LHR promoter activity was detected in HeLa cells, indicating a cell specific nature of its function. The first 173 bp promoter domain is GC-rich, with several SP-1 binding domains, and it bound specifically nuclear proteins isolated from mLTC-1 and HeLa cells. RNAse protection assays reconfirmed the presence of several transcription initiation sites within the first 310 bp of the 5'-UTR, also in the absence of the cognate LHR coding sequences. The most distal site at bp -310 did not function in the absence of the first 173 bp of the 5'-UTR. Other transcription initiation sites were identified closer to the translation initiation site. hCG (50 micrograms/l), 8-bromo (Br)-cAMP (100 mumol/l) and cholera toxin (100 microgram/l) displayed qualitatively similar negative effects on the LHR promoter activity in the transfected mLTC-1 cells when the constructs containing at least the first 565 bp of the LHR 5'-UTR were used, but the inhibitory effects were greatly decreased in constructs containing < or = 304 bp of the promoter region. Hence, the hCG/cAMP associated inhibitory effects interact with region(s) located mainly between bp -565 and -305 of the LHR promoter. The inhibitory role of cAMP on LHR gene expression was also confirmed at the level of hCO-binding and hCG stimulated cAMP production of mLTC-1 cells. In conclusion, the current results elucidate the cis- and trans-acting elements in the regulation of expression of the murine LHR gene in cultured mouse Leydig cells. The minimal basal promoter activity is within the first 173 nucleotides of the 5'-UTR and the structural elements of the negative LHR regulation by the cognate hormone and elevated cAMP levels are mainly located within nucleotides -305 to -565 of the 5'-UTR. The function of the murine LHR promoter is similar to, though not identical with that of the rat, but at variance with that of the human LHR gene.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1996

Salivary progesterone concentrations after tubal sterilization.

OBJECTIVE: To find out if ovarian endocrine function is hampered by laparoscopic tubal sterilization. METHODS: Salivary progesterone levels were measured in 55 women undergoing a laparoscopic tubal sterilization with Hulka or Filshie clips. The participants were 31-43 years old (mean 37) and were menstruating regularly. The saliva was collected every morning during three menstrual cycles: on the cycle preceding sterilization, and 3 and 12 months after the procedure. Salivary progesterone levels were determined by a radioimmunoassay. RESULTS: Total progesterone secreted in the luteal phase declined slowly after the sterilization, resulting in the lowest values 1 year after the procedure (1780 +/- 807 versus 2431 +/- 1187 pmol/L before surgery, P = .001). The luteal peak progesterone values were lowest 3 months after sterilization (277 +/- 137 pmol/L). Although the peak progesterone secretion seemed to have started to recover at 12 months (318 +/- 171 pmol/L), it was still significantly less than before surgery (378 +/- 150 pmol/L, P = .015). The length of the entire menstrual cycle and the lengths of the follicular and luteal phases were not affected. CONCLUSION: Although the menstrual pattern was not affected, laparoscopic tubal sterilization caused measureable changes in the luteal function. However, these changes may be temporary in nature.

Adult↗
PubMed1996

A case of hypergonadotrophinaemia associated with very high isolated concentrations of immunologically and biologically active luteinizing hormone.

A very rare case of a menstruating infertile woman with isolated luteinizing hormone (LH) hypergonadotrophinaemia is presented. There were no signs indicating the presence of a pituitary microadenoma, and LH had normal bioactivity and normal molecular weight. Likewise, no mutation was detected in the coding region of the LH beta-chain gene. In a non-stimulated cycle and a clomiphene citrate cycle, the patient developed an unruptured cyst. The patient ovulated and conceived twice following the addition of human chorionic gonadotrophin. A partial resistance at the ovarian LH receptor site, perhaps caused by a mutation, is a possible explanation for these findings. Another possibility is a malfunction in the signal transduction system of LH beyond the receptor level.

Adult↗
PubMed1996

Failure of spermatogenesis to recover despite the presence of a spermatogonia in the irradiated LBNF1 rat.

The dose and time response of LBNF1, rat testis to gamma irradiation was studied with use of single doses from 2.5 Gy to 6.0 Gy. Germ cells were initially depleted as a result of killing the radiosensitive differentiating spermatogonia. Some recovery of spermatogenesis was observed at 4 and 6 wk after irradiation as indicated by the repopulation of tubules with germ cells derived from surviving stem spermatogonia. Although spermatogenesis showed additional recovery and was maintained throughout the 60-wk follow-up period after 2.5 Gy, at doses from 3.5 Gy to 6.0 Gy, repopulation indices declined after 6 wk to less than 2%. The numbers of Sertoli cells per nonrepopulating tubule were constant, independent of radiation dose or time. In addition, the nonrepopulating tubules contained an average of one A spermatogonium per 100 Sertoli cells. The size and shape of these cells corresponded to undifferentiated A spermatogonia in nonirradiated control tests. Despite high labeling (40%) and mitotic (20%) indices, the numbers of A spermatogonia changed very little with time, and no differentiated cells were produced in these tubules. The failure of spermatogenesis to recover was not due to hormone deficiency: serum gonadotropin levels increased after irradiation, and serum testosterone remained at control levels. The irradiated LBNF1 rat model may be useful for studying the regulation of differentiation of A spermatogonia.

Animals↗
PubMed1996

Induction of lipid peroxidation during steroidogenesis in the rat testis.

Free radical production and lipid peroxidation are potentially important mediators in testicular physiology and toxicology. The cytochrome P450 enzymes of the steroidogenic pathway are known to produce free radicals. The present study was conducted to elucidate in vivo the gonadotropin regulation of free radical-mediated lipid peroxidation and the antioxidative defense system in the rat testis. GnRH antagonist (Org 30276; 1 mg/kg BW) and testosterone [40-mm SILASTIC brand (Dow-Corning) capsules] treatments were used to suppress serum gonadotropin levels. As expected, serum LH decreased to a very low level, whereas serum FSH decreased only slightly. Testosterone treatment for 8 days decreased the levels of the peroxide-metabolizing enzymes, catalase, glutathione peroxidase (GSH-Px), and glutathione transferase (-44%, -24%, and -31%, respectively; P < 0.01 for all). These changes predominately reflect the interstitial tissue, in which catalase and GSH-Px activities were much higher than in the seminiferous tubules. Testicular CuZn or Mn superoxide dismutase activities, which were high in the seminiferous tubules, were not affected by gonadotropin suppression. The total peroxyl radical-trapping capacity of the testis, or its components, vitamin E and ubiquinol 9, were not affected either. Lipid peroxidation was decreased after 8-day treatment, as detected by diminished formation of conjugated dienes and fluorescent chromolipids (-30% and -19%, respectively; P < 0.05 for both). Similar results of decreasing catalase and GSH-Px activities were found after gonadotropin suppression with GnRH antagonist treatment for 2 days or testosterone treatment for 5 days. Substitution with hCG, alone or in combination with recombinant human FSH, reversed the changes in enzyme activities, whereas FSH alone had no effect. After 5-day testosterone treatment, catalase messenger RNA expression was studied by Northern hybridization, and it was observed to parallel the changes in enzyme activity. The site of free radical production was studied by separating interstitial tissue and seminiferous tubules 5 h after hCG injection. GSH-Px was induced by hCG only in the interstitial tissue (+28%; P< 0.01), supporting the hypothesis of free radical production during steroidogenesis. Aminoglutethimide, an inhibitor of the P450 cholesterol side-chain cleavage enzyme, induced extensive lipid peroxidation in the testis. Presumably, aminoglutethimide leads to leakage of free radicals from the P450 enzyme when substrate oxygenation is prevented. In conclusion, the present study suggests that physiological LH action in the rat testis causes lipid peroxidation and maintains high activities of peroxide-metabolizing enzymes in the interstitial tissue.(ABSTRACT TRUNCATED AT 400 WORDS)

Aminoglutethimide↗
PubMed1996

Suppression of mouse spermatogenesis by a gonadotropin-releasing hormone antagonist and antiandrogen: failure to protect against radiation-induced gonadal damage.

A combined GnRH antagonist (Nal-Glu) and antiandrogen (flutamide) treatment was used to suppress mouse spermatogenesis in an attempt to enhance recovery from stem cells after irradiation, as observed previously in the rat. Two weeks of treatment suppressed the intratesticular testosterone concentration to 10% of the control value, decreased testicular weight to 16% of the control value, and sperm count 2600-fold. Suppression was at least as great as that produced in the rat by Nal-Glu-flutamide. Testicular weights, sperm counts, and histology were indistinguishable from those in normal controls 45 days after the end of the treatment. Despite the suppression of spermatogenesis, the treatment did not enhance recovery of spermatogenesis after damage produced by a 10-Gray dose of radiation; 45 days after irradiation, testicular weight, sperm head counts, and repopulation indexes were as low as in the mice that received no hormone treatment. In contrast to the situation in the rat, after irradiation of mice, almost no A spermatogonia were found in the 80% non-repopulating tubules, indicating that nearly all A spermatogonia remaining after irradiation were capable of differentiation. This absence of A spermatogonia that fail to differentiate in the mouse is proposed as the reason for failure to protect against radiation-induced gonadal damage by hormone treatment.

Androgen Antagonists↗
PubMed1996

Depletion and repopulation of Leydig cells in the testes of aging brown Norway rats.

The capacity of Brown Norway rat Leydig cells to produce testosterone has been shown to decrease with aging. Our objectives herein were to determine 1) whether ethane dimethanesulfonate (EDS) administration would eliminate the hypofunctional Leydig cells of the aged Brown Norway rat testis; 2) if so, whether a new generation of Leydig cells subsequently would appear; and 3) if so, whether the steroidogenic capacity of the new Leydig cells would be at the relatively low level of the cells they replaced or at the high level of young adult Leydig cells. Young (3-month-old) and aged (18-month-old) rats received an injection of EDS (8.5 mg/100 g BW). One, 5, and 10 weeks thereafter, the serum testosterone concentration and the capacity of the testes and of isolated Leydig cells to produce testosterone were determined. One week after EDS treatment, Leydig cells were not seen in the testes of young or aged rats, and the serum testosterone concentration and testicular testosterone production were reduced to undetectable levels. Five weeks after EDS treatment, serum testosterone levels at both ages were restored to those in age-matched controls, and the capacity of the testes to produce testosterone was restored partially (young rats) or completely (aged rats). By 10 weeks after EDS treatment, the serum testosterone concentration in young rats and the ability of their testes to produce testosterone were at the levels of age-matched controls. In aged rats, however, serum testosterone and testicular testosterone production were at levels that significantly exceeded those of aged-matched controls and, indeed, were not significantly different from those of young control or EDS-treated rats. Consistent with this, the ability of Leydig cells isolated from the testes of young rats and that of cells from aged rats to produce testosterone 10 weeks after the rats were treated with EDS were equivalent. The enhanced ability of the Leydig cells restored to the aged testes to produce testosterone was not a consequence of exposure to increased levels of LH. Thus, although situated in an aged testis and in the environment of an aged hypothalamic-pituitary axis, the steroidogenic function of the Leydig cells restored to aged rat testes was equivalent to that of young rat Leydig cells.

Aging↗