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PubMed1978

Experimental autoimmune orchitis in T-cell-deficient mice.

Experimental autoimmune orchitis (EAO) was induced in inbred strains of mice by injection of mouse testis homogenate (MTH) in Freund's complete adjuvant with pertussis vaccine. Although all mice injected with MTH and adjuvants developed signs of EAO, there were marked strain variations in susceptibility to EAO suggesting that genetic factors may be involved in the response to antigen or to adjuvants. Studies in hypothymic BALB/c. nu/nu mice indicated that a source of T cell was required for induction of EAO. Thus BALB/c. nu/nu mice were not able to develop EAO, despite adequate orchitogenic challenge; reconstitution of nu/nu mice with syngeneic thymocytes completely restored the capacity of such mice to develop orchitis. Transfer of EAO was effected in nu/nu mice with lymphoid cells from appropriately immunized donors but not with immune serum. However, both T cells and antibodies may be necessary in the effector stages of the disease since the capacity of lymphoid cells to transfer EAO was only partially inhibited by anti-Thy-1.2 treatment.

Animals↗
PubMed1998

Pex mRNA is localized in developing mouse osteoblasts and odontoblasts.

Mutations in PEX, a phosphate-regulating gene with homology to endopeptidase on the X chromosome, were recently identified in patients with X-linked hypophosphatemia (XLH), an inherited disorder of phosphate homeostasis characterized by growth retardation and rachitic and osteomalacic bone disease. To understand the mechanism by which loss of PEX function elicits the mutant phenotype, a study of its mRNA localization and ontogenesis was undertaken. Using the reverse transcriptase-nested polymerase chain reaction (RT-nested PCR) with polyA+ RNA purified from mouse testis, a 337-bp Pex cDNA fragment was generated and cloned in the pCRII plasmid. The cDNA was used to generate sense and anti-sense Pex riboprobes for in situ hybridization (ISH) and Northern analysis. To survey a large number of different tissues, sagittal sections of embryos and newborn mice were examined. ISH showed the presence of Pex mRNA in osteoblasts and odontoblasts. Pex gene expression was detectable on Day 15 of embryonic development, which coincides with the beginning of intercellular matrix deposition in bones. Finally, Northern analysis of total RNA from calvariae and teeth of 3-day-old and adult mice showed that the abundance of the 7-kb Pex transcript is decreased in adult bones and in nongrowing teeth. The present study demonstrates that Pex mRNA is expressed in bones and teeth and suggests that this putative endopeptidase plays an important role in the development of these tissues.

Aging↗
PubMed2003

Dynamics of testicular germ cell apoptosis in normal mice and transgenic mice overexpressing rat androgen-binding protein.

The number and type of testicular germ cells undergoing apoptosis in different age groups of mice (from 7 to 360 days of age) was determined and compared in age-matched wild type (WT) control and in a transgenic (TG) mice homozygous to rat androgen binding protein (ABP) using flow cytometry. Flow cytometric quantification revealed that the total number of germ cells undergoing apoptosis did not differ significantly in WT and TG mice up to Day 14. From Day 21 to Day 60, the number of germ cells undergoing apoptosis was consistently higher in TG than in WT mice. Starting from Day 90, the number of germ cells undergoing apoptosis in TG mice was lower than controls until Day 360. In 21-60 days old TG mice, spermatogonia, S-Phase cells, and primary spermatocytes are the cell types undergoing apoptosis at significantly greater numbers than those in WT mice. However, starting from day 60, the total number of spermatids undergoing apoptosis was significantly lower in TG mice than in age-matched WT controls. TdT-mediated dUTP-biotin nick end labeling (TUNEL) in testicular sections from TG mice of 21 and 30 days of age confirmed the presence of increased numbers of apoptotic germ cells compared to their age matched controls. These data indicate that the continuous presence of greater than physiological concentrations of ABP in the mouse testis has a biphasic effect on the frequency of apoptosis in germ cells. The initial pre-pubertal increase in testicular germ cell apoptosis may result from direct or indirect actions of ABP and is likely to determine the subsequent life-death balance of germ cell populations in TG mice, whereas the subsequent reduction may result from maturation depletion. A wave of apoptosis during the pre-pubertal period is required for normal spermatogenesis to develop, and our data indicate that this apoptotic wave may be regulated by ABP and/or androgens.

Acetates↗
PubMed1986

Tissue and species specificity of unmasked nuclear acceptor sites for the estrogen receptor of Squalus testes.

The testicular estrogen receptor of the shark Squalus acanthias is restricted to nuclear subfractions when tissue is homogenized in low salt buffers and adheres tightly to nuclei and DNA-cellulose even when exposed to high salt conditions. Therefore, we examined the binding characteristics of this receptor to chromatin subfractions from homologous and heterologous tissues. Squalus chromatin linked to cellulose and partially deproteinized by 0-8 M guanidine hydrochloride (GuHCl) gave extraction patterns similar to those obtained with mammalian and avian chromatin. Chromatin as prepared in our laboratory contained no bound estrogen receptor. The binding pattern of the [3H]estradiol-labeled nuclear estrogen receptor to chromatin fractions from Squalus testicular zones I/II (containing spermatogonia, spermatocytes, and high receptor levels) revealed maximal binding activity (acceptor sites) on chromatin previously extracted with 2-4 M GuHCl (350% increase over unextracted chromatin), with a 40% decrease from maximal binding at 5-8 M GuHCl. By contrast, binding to chromatin from zone III (containing spermatozoa and little or no detectable receptor) showed no major peak and 4 times less binding at 3 M GuHCl-extracted chromatin. We have previously shown that zones I and II contain the majority of testicular receptors and, presumably, are the primary sites of estrogen action, whereas receptor activity in zone III is minimal (less than 5%), indicating a secondary or nontarget tissue. Squalus testicular [3H]estradiol-receptor complexes bound minimally to rabbit uterine chromatin. Likewise, [3H]estradiol-receptor complexes from rabbit uterus, Squalus oviduct, or mouse testis bound minimally to Squalus testicular chromatin. Thus, maximal binding occurred only with Squalus zones I/II chromatin and Squalus testicular receptor. The binding of [3H]estradiol-receptor complexes to testicular chromatin (zones I/II) was of high affinity (Kd = 1.9 X 10(-10) M) and low capacity and was optimal in the presence of 150 mM KCl, but was unaffected by the addition of urea in an amount similar to that of Squalus body fluids (300 mM). [3H]Estradiol binding to chromatin required undenatured receptor and was competitively inhibited by radioinert estradiol-receptor complexes, confirming saturability of acceptor sites. The affinity of the Squalus estrogen receptor for homologous chromatin was in the same range as that reported for other systems, despite the unusual nuclear extractability characteristics of Squalus receptor. This study provides new evidence for tissue and species specificity of receptor binding to chromatin acceptor sites.

Animals↗
PubMed2001

Irradiation selectively inhibits expression from the androgen-dependent Pem homeobox gene promoter in sertoli cells.

How radiation blocks spermatogenesis in certain strains of rats, such as LBNF(1), is not known. Because the block depends on androgen, we propose that androgen affects Sertoli cell function in irradiated LBNF(1) rats, resulting in the failure of spermatogonial differentiation. To begin to identify genes that may participate in this irradiation-induced blockade of spermatogenesis, we investigated the expression of several Sertoli genes in response to irradiation. The expression of the PEM: homeobox gene from its androgen-dependent Sertoli-specific proximal promoter (Pp) was dramatically reduced more than 100-fold in response to irradiation. In contrast, most other genes and gene products reported to be localized to the Sertoli cell, including FSH receptor (FSHR), androgen receptor (AR), SGP1, and the transcription factor CREB, did not exhibit significant changes in expression, whereas transferrin messenger RNA (mRNA) expression dramatically increased in response to irradiation. Irradiation also decreased Pp-driven PEM: mRNA levels in mouse testes (approximately 10-fold), although higher doses of irradiation than in rats were required to inhibit PEM: gene expression in testes of mice, consistent with their greater radioresistance. The decrease in Pem gene expression in mouse testis was also selective, as the expression of CREB, GATA-1, and SGP1 were little affected by irradiation. We conclude that the dramatic irradiation-triggered reduction of Pem expression in Sertoli cells is a conserved response that may be a marker for functional changes in response to irradiation.

Androgens↗
PubMed1989

Expression and regulation of the proenkephalin gene in rat Sertoli cells.

Previous studies have shown that multiple forms of proenkephalin RNA are present in the rat and mouse testis that are cell type specific: a 1700-nucleotide transcript, unique to the testis, found in spermatogenic cells, and a 1450-nucleotide form of somatic cell origin. In the present studies, rat Sertoli cells are shown to contain the 1450-nucleotide form of proenkephalin RNA. The concentration of this transcript is quite low immediately after Sertoli cell isolation, but increases after 1 day in culture to a constant level. Proenkephalin RNA levels are stimulated severalfold by FSH and cAMP, but are not significantly affected by LH or testosterone. These studies demonstrate that Sertoli cells are at least one source of the somatic, 1450-nucleotide form of proenkephalin RNA in the rat testis. The expression of opioid peptide genes by Sertoli cells as well as by germ and Leydig cells is further evidence for the postulated autocrine or paracrine functions of these peptides in the testis.

1-Methyl-3-isobutylxanthine↗
PubMed1993

Isolation of the murine cyclin B2 cDNA and characterization of the lineage and temporal specificity of expression of the B1 and B2 cyclins during oogenesis, spermatogenesis and early embryogenesis.

A cDNA encoding the murine cyclin B2 (cycB2) was isolated from an adult mouse testis cDNA library as part of studies designed to identify cyclins involved in murine germ cell development. This cycB2 cDNA was then used to examine the pattern of cycB2 expression during male and female germ cell development and in early embryogenesis, and to compare this expression with the previously characterized expression of cycB1. A single 1.7 kb cycB2 transcript was detected by northern blot hybridization analysis of total RNA isolated from midgestation embryos and various adult tissues. Northern blot and in situ hybridization analyses revealed that cycB2 expression in the testis was most abundant in the germ cells, specifically in pachytene spermatocytes. This is in contrast to the highest levels of expression of cycB1 being present in early spermatids. In situ analysis of the ovary revealed cycB2 transcripts in both germ cells and somatic cells, specifically in the oocytes and granulosa cells of growing and mature follicles. The pattern of cycB1 and cycB2 expression in ovulated and fertilized eggs was also examined. While the steady state level of cycB1 and cycB2 signal remained constant in oocytes and ovulated eggs, signal of both appeared to decrease following fertilization. In addition, both cycB1 and cycB2 transcripts were detected in the cells of the inner cell mass and the trophectoderm of the blastocyst. These results demonstrate that there are lineage- and developmental-specific differences in the pattern of the B cyclins in mammalian germ cells, in contrast to the co-expression of B cyclins in the early conceptus.

Animals↗
PubMed2000

Dynein light chain interacts with NRF-1 and EWG, structurally and functionally related transcription factors from humans and drosophila.

Nuclear respiratory factor-1 is a transcriptional activator that has been implicated in the nuclear control of respiratory chain expression. Yeast two-hybrid screens were performed to identify proteins that physically interact with nuclear respiratory factor-1. Saturation screening of both mouse embryo and mouse testis libraries yielded 14 independent clones, all of which represented two different isoforms of dynein light chain. In addition to using the two-hybrid method, the specificity of the nuclear respiratory factor-1/dynein light chain interaction was established by chemical crosslinking of the purified native proteins and by co-immunoprecipitation of nuclear respiratory factor-1 and dynein light chain from mammalian cells. Both two-hybrid and chemical crosslinking assays demonstrated that binding of dynein light chain required the first 26 amino acids of nuclear respiratory factor-1. Although dynein light chain is associated with dynein, a cytoplasmic motor molecule, immunolocalizations showed substantial nuclear staining using several different anti-dynein light chain antibodies. Moreover, fluorescence overlays of confocal images established that nuclear respiratory factor-1 and dynein light chain displayed a very similar nuclear staining pattern. The significance of the nuclear respiratory factor-1/dynein light chain interaction was investigated further by determining whether a similar interaction was conserved between dynein light chain and the erect wing gene product of Drosophila, a protein related to nuclear respiratory factor-1 through its DNA binding domain. Here, we establish that the erect wing gene product can bind and trans-activate transcription through authentic nuclear respiratory factor-1 binding sites. Moreover, the erect wing gene product, like nuclear respiratory factor-1, interacted specifically with dynein light chain both in vitro and in transfected cells. Thus, the interaction with dynein light chain is conserved between transcription factors that are structurally and functionally similar between humans and Drosophila.

Animals↗
PubMed2001

M31 and macroH2A1.2 colocalise at the pseudoautosomal region during mouse meiosis.

Progression through meiotic prophase is associated with dramatic changes in chromosome condensation. Two proteins that have been implicated in effecting these changes are the mammalian HP1-like protein M31 (HP1beta or MOD1) and the unusual core histone macroH2A1.2. Previous analyses of M31 and macroH2A1.2 localisation in mouse testis sections have indicated that both proteins are components of meiotic centromeric heterochromatin and of the sex body, the transcriptionally inactive domain of the X and Y chromosomes. This second observation has raised the possibility that these proteins co-operate in meiotic sex chromosome inactivation. In order to investigate the roles of M31 and macroH2A1.2 in meiosis in greater detail, we have examined their localisation patterns in surface-spread meiocytes from male and female mice. Using this approach, we report that, in addition to their previous described staining patterns, both proteins localise to a focus within the portion of the pseudoautosomal region (PAR) that contains the steroid sulphatase (Sts) gene. In light of the timing of its appearance and of its behaviour in sex-chromosomally variant mice, we suggest a role for this heterochromatin focus in preventing complete desynapsis of the terminally associated X and Y chromosomes prior to anaphase I.

Animals↗
PubMed1982

A re-evaluation of the relationships between the fibrillar centres and the nucleolus-organizing regions in reticulated nucleoli: ultrastructural organization, number and distribution of the fibrillar centres in the nucleolus of the mouse Sertoli cell.

In mouse testis, the diploid Sertoli cell displays one large nucleolus flanked symmetrically by two heterochromatic masses. The hybridization in situ with [3H]rRNA confirmed that the ribosomal cistrons are localized with in the central nucleolar mass. At the ultrastructural level this nucleolar mass appears to be reticulated and contains numerous fibrillar centres. These fibrillar centres are surrounded and interconnected by an electron-opaque fibrillar network, which constitutes the reticulated nucleolonema of the nucleolus. Ag--NOR staining reveals the presence of the argyrophilic proteins associated with active nucleolus-organizing regions (NORs) within both the fibrillar centres and the electron-opaque fibrillar component. Autoradiographic studies after [3H]uridine incorporation show that ribosomal DNA transcription only takes place in this dense fibrillar component. Three-dimensional reconstruction of four Sertoli cell nucleoli after serial sectioning reveals that the size and number of the fibrillar centers are very variable from one cell to another (26, 35, 38 an 41 fibrillar centres). The analysis of the volume occupied by the fibrillar centres as compared to the whole nucleolar volume demonstrates that the larger the nucleolus, the more fibrillar centres it contains, but also the more numerous the fibrillar centres, the larger their total volume. While in each case the number of the NORs is virtually the same, i.e. ten. In the light of these results we concluded that, at least in reticulated nucleoli, there is no numerical relationship between the number of fibrillar centres and the number of NORs, and that the fibrillar centers cannot be considered only as the nucleolar counterparts of the NORs. Moreover, the increasing number of fibrillar centres from the smallest nucleolus to the largest one is difficult to explain by the previously postulated hypothesis of a reserve of inactive rDNA packaged in the fibrillar centers. These data led us to reconsider the role of the fibrillar centres in the transcriptional activity of reticulated nucleoli.

Animals↗
PubMed1989

Analysis of the expression of two phosphoglycerate kinase genes in a mouse cultured cell line during activation and inactivation of the c-myc gene.

The effect of a change in the concentration of c-myc protein on the expression of genes for two phosphoglycerate kinase isozymes was investigated. The steady state levels of messenger ribonucleic acids (mRNAs) for sperm-type and non-sperm-type proteins were determined by blot hybridization using the RNA of the mouse cell line 38-2 containing the inducible rat c-myc gene cultured under various conditions. Without induction the c-myc gene. mRNA for non-sperm-type protein was detected at a level that remained essentially constant during both activation and inactivation of the c-myc gene. mRNA for sperm-type protein was not detected in 38-2 cells cultured under any conditions used. Change in the amount of c-myc protein alone does not appear to bring about a switch of the expression of the two phosphoglycerate kinase genes during spermatogenesis in mouse testis.

Cell Line↗
PubMed1988

Flow cytometric evaluation of the effects of 2.3 MeV neutrons and 240 kV X rays on mouse spermatogenic S-phase cells using bromodeoxyuridine incorporation.

A sensitive flow cytometric assay has been developed to assess the effect of X rays or neutrons on the DNA-synthesizing ability of mouse testis cells. The dose to reduce the labelling index (LI) to 50% (ED50) was 25 cGy for X rays and 5 cGy for neutrons, giving a relative biological effectiveness (RBE) of 5.0. A significant reduction of the LI was seen at X-ray doses as low as 10 cGy. Neutron treatment resulted in an exponential decrease in functional S-phase cells while the X-ray response was biphasic. The sensitivity and rapidity of the assay would be suitable for use in biological dosimetry.

Animals↗
PubMed1999

Changes in lectin binding patterns of mouse male germ cells (gonocytes) during prespermatogenesis.

The distribution of sugar residues in gonocytes of the differentiating mouse testis was examined by light microscopy using 22 different kinds of lectins. Characteristic binding patterns of sWGA, VVA, and LEA in gonocytes were observed during prespermatogenesis. sWGA preferentially bound to the cytoplasm and plasma membrane of gonocytes on 16.5 days post coitus (dpc). Its reaction decreased thereafter and almost disappeared on 1.5 days post partum (dpp), but reaction reappeared on 4.5 dpp and continued until 6.5 dpp. The VVA reaction was recognized in a few gonocytes on 0.5 dpp, and remained strong until 6.5 dpp. LEA reacted strongly in the plasma membrane and cytoplasm of gonocytes from 0.5 dpp to 6.5 dpp. The present study indicates that sWGA, VVA, and LEA are useful markers for gonocytes, and the appearance or disappearance of sWGA and VVA may be related to the differentiation of gonocytes during prespermatogenesis.

Aging↗
PubMed1983

Qualitative and quantitative changes in plasma luteinizing hormone (LH) under stimulation by intravenous infusion of synthetic luteinizing hormone-releasing hormone (LHRH) in Japanese monkeys (Macaca fuscata) as assessed by electrofocusing.

Using 5 adult Japanese monkeys (Macaca fuscata) of both sexes, the qualitative and quantitative changes in plasma LH caused by LHRH administration were examined before and after castration. Five hundred micrograms synthetic LHRH was infused for 2 hrs and blood samples were obtained every 15 min for 5 hrs under ketamine hydrochloride anesthesia. Plasma LH levels were determined by an in vitro bioassay using the mouse testis interstitial cell preparation. The LHRH infusion induced a biphasic release of LH in intact animals of both sexes and in castrated females but not in castrated males. The biphasic pattern of LH release was characterized by an initial acute rise followed by a plateau or a fall and the consecutive second rise after a long latent period. Aliquots of plasma samples obtained during 30-90 (corresponding to the initial rise) and 120-210 min (corresponding to the second rise) after the initiation of LHRH infusion were pooled separately (plasma pools I and II, respectively) and subjected to isoelectrofocusing (IEF) fractionation. The IEF fractionation was performed in ampholine-sucrose gradient, pH range 3.5-10, under a constant electrical power supply (3 W, 700 V) for 48 hrs at 4 degrees C. After the completion of the IEF fractionation the LH activity in each fraction was measured by the in vitro bioassay. The IEF fractionation separated plasma LH into 6 distinct species in terms of pI values. When the IEF profiles of plasma pools I and II in intact animals of both sexes were compared, the increase and the decrease in acidic to neutral LH and alkaline LH, respectively, were consistent and significant in plasma pool II. Changes of the same kind were further exaggerated when the IEF profiles in castrated animals were compared with those in non-castrated ones. The acidic LH may represent the LH species newly synthesized and not well processed. The LH species possessing pI values of 7.5-8.5 is likely to be the mature type of LH exhibiting high biological potency. The LH species migrating in the high alkaline region seems to be the LH of over-maturation.

Animals↗
PubMed1978

Branched-chain amino acid aminotransferase in mouse testicular tissue.

Branched-chain amino acid aminotransferase (L-leucine:2-oxoglutarate aminotransferase, EC 2.6.1.6) activity was determined in several tissues of the mouse. Testis homogenates presented a specific activity very close to that of heart extracts which were the most active. Enzyme activity was detectable in testes from 5-day-old mice and increased steadily during development to reach a maximum at the 20th day of life. The transaminase was present in the cytosol of testicular homogenates and also associated, probably in the matrix, with a special type of mitochondria present in spermatozoa and gametogenic cells. The enzyme from testis is active against the three branched-chain amino acids and catalyses the reaction in both directions. Highest activity and lowest Km were obtained with L-leucine. Activity with L-valine was the lowest. The enzyme from the mitochondrial fraction showed identical properties to that from the soluble phase. The possible participation of this aminotransferase in a shuttle system transferring reducing equivalents from cytoplasm to mitochondria is postulated.

Animals↗
PubMed1981

An electrophoretically detectable modification of glucosephosphate isomerase in mouse spermatozoa.

Cellulose acetate electrophoresis of glucosephosphate isomerase (GPI) from mouse testis and spermatozoa revealed a minor band which is not seen in electropherograms of GPI from other tissues. The minor band is associated equally with the two electrophoretic variants of GPI examined. Treatment of tissue extracts with various enzymes, enzyme inhibitors or thiol reagents failed to alter the appearance or position of the minor bands in sperm and testis GPI, or to induce their appearance in GPI from other tissues. No minor bands were seen in electropherograms of testis GPI from immature males, or from males whose testes lack spermatozoa for genetic reasons.

Animals↗
PubMed1991

Proliferative activity of gonocytes, Sertoli cells and interstitial cells during testicular development in mice.

Developing mouse testis was studied from Day 14 post coitum (p.c.) until Day 35 post partum (p.p.) by [3H]thymidine autoradiography. The gonocytes proliferated actively at Day 14 p.c., the [3H]thymidine labelling index (L.I.) being 7.5%, and were quiescent from Day 16 p.c. up to the first day of life, when spermatogenesis started. The L.I. increased to 20% at Day 2 p.p. The L.I. for the Sertoli cells was approximately 20% before birth. After birth the proliferative activity decreased. After Day 11 p.p., the Sertoli cells showed their typical adult appearance. After Day 17 p.p. no labelled Sertoli cells were observed. The Leydig cells featured a very low proliferative activity up to Day 21 p.p. (L.I. of maximal 1.9%). At Day 29 p.p. there was a peak of 7.4% in L.I., followed by a sharp decrease to 0.35% at Day 35 p.p. The L.I. of mesenchymal cells decreased from 11.4% at Day 14 p.c. to 1.1% at Day 14 p.p. and remained more or less constant thereafter. The proliferative activity of myoid, endothelial and perivascular cells followed a similar course to that of mesenchymal cells, their L.I.s being high before birth (16, 12.5 and 19%, respectively, decreasing until Day 14 p.p. (0.6, 2.0 and 1.2%, respectively) and thereafter being more or less constant. There was an increase in the relative number of Leydig cells from approximately 4% of the total interstitial cell number at Day 14 p.p. to 29.5% at Day 35 p.p. At the same time, the relative number of mesenchymal cells decreased from 55 to 13%. The diameter of the seminiferous tubules showed a peak of 92 microns at Day 16 p.c., decreased to 44 microns at Day 1 p.p. and increased again to 204 microns at Day 33 p.p. These results show that, except for the Leydig cells, the proliferative activity of testicular cell types is highest during the pre- and early postnatal period. The major outgrowth of the Leydig cell population occurs around the fourth week after birth. The results are in accordance with the hypothesis that the mesenchymal cells are the progenitors of Leydig cells.

Animals↗
PubMed1990

Effect of LH injections on testicular steroidogenesis, cholesterol side-chain cleavage P450 mRNA content and Leydig cell morphology in hypogonadal mice.

Hypogonadal (hpg) mice have a congenital deficiency of hypothalamic gonadotrophin-releasing hormone (GnRH) and the gonads consequently lack exposure to gonadotrophins during development. We injected male hpg mice with LH for 10 days to investigate whether LH alone can stimulate normal steroidogenesis in these animals. Control animals had an inactive interstitium and very few germ cells. Testicular content of androgens was undetectable by radioimmunoassay in control animals unless a single injection of LH was given 1 h before death, when androgens were just detectable. Control testes incubated in vitro with [3H]pregnenolone demonstrated that without gonadotrophin stimulation pregnenolone was metabolized only to progesterone in significant amounts. Assay for cholesterol side-chain cleavage cytochrome P450 (P450scc) mRNA showed basal expression in saline-treated hpg mouse testis. LH treatment induced hypertrophy and hyperplasia of Leydig cells and division of germ cells. Testicular androgen content increased significantly, with testosterone and androstenedione as the major androgens. LH-treated testes incubated with [3H]pregnenolone in vitro had a greater synthetic capacity for testosterone, suggesting an increase in 17 alpha-hydroxylase/C17-20-lyase activity. Basal and human chorionic gonadotrophin-stimulated androgen production in vitro increased markedly following LH treatment to levels previously described in the normal adult animal. LH treatment caused a rapid and transient increase in the hybridization of P450scc mRNA which was sevenfold greater than that of saline-treated controls when the animals were killed 1 h after the last injection but fell to control levels within 24 h of cessation of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Androgens↗