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Pax-5 encodes the transcription factor BSAP and is expressed in B lymphocytes, the developing CNS, and adult testis.

BSAP has been identified previously as a transcription factor that is expressed at early, but not late, stages of B-cell differentiation. Biochemical purification and cDNA cloning has now revealed that BSAP belongs to the family of paired domain proteins. BSAP is encoded by the Pax-5 gene and has been highly conserved between human and mouse. An intact paired domain was shown to be both necessary and sufficient for DNA binding of BSAP. Binding studies with several BSAP recognition sequences demonstrated that the sequence specificity of BSAP differs from that of the distantly related paired domain protein Pax-1. During embryogenesis, the BSAP gene is transiently expressed in the mesencephalon and spinal cord with a spatial and temporal expression pattern that is distinct from that of other Pax genes in the developing central nervous system (CNS). Later, the expression of the BSAP gene shifts to the fetal liver where it correlates with the onset of B lymphopoiesis. BSAP expression persists in B lymphocytes and is also seen in the testis of the adult mouse. All of this evidence indicates that the transcription factor BSAP may not only play an important role in B-cell differentiation but also in neural development and spermatogenesis.

Amino Acid Sequence

Leydig cell development in the pig testis during the late fetal and early postnatal period: an electron microscopic study with attention to the influence of fetal decapitation.

The ultrastructure of fetal and postnatal pig Leydig cells was studied from 75 days postcoitum (p.c.) to 1 month after birth. Additionally, decapitated fetuses from 75 days p.c. until birth were used to study the effect of deprivation of gonadotrophins on the ultrastructure of Leydig cells. Normal Leydig cell development was characterized by a change in smooth endoplasmic reticulum (SER). Next to branched tubular SER, whirls of elaborate and tightly packed SER membranes appeared. The amount of SER increased with age but decreased slightly before the end of the observation period. Rough endoplasmic reticulum (RER) was a minor component. Large bundles or whirls of intermediate filaments were abundant until just before birth; thereafter, they decreased drastically. Peroxisome-like structures and crystalloid bodies were observed with increasing frequency from 75 days p.c. and 20 days postpartum onward. Polygonal lysosome-like dense bodies transformed into complex membranous structures especially after birth. Giant mitochondria occurred in the late fetal and postnatal period. From 75 days p.c. onward fully developed Leydig cells were scarce in testes of decapitated fetuses. Leydig cell characteristics disappeared toward the end of the fetal period; only the cell shape, the large bundles or whirls of intermediate filaments, some scarce polygonal lysosome-like dense bodies, and RER remained, but SER was negligible. Progressive hemorrhages apparent in situ were correlated positively with fetal age. The dependency of Leydig cells upon LH began between 60 and 75 days postcoitum.

Animals

Effect of embryonic and/or neonatal diethylstilbestrol and allylestrenol treatment on postnatal development of the chick testis.

The synthetic steroid diethylstilbestrol (DES) and the steroid-like allylestrenol (AE) have been used for years in human medicine for the protection of pregnancy. The hazards to the fetus of gestational DES treatment are well established [2, 17, 18]. Knowledge of a similar effect of AE is still fragmentary. Therefore, further studies are required of the after-effects of embryonic and perinatal AE exposure. In our earlier experiments with polypeptide hormones [4, 5, 6] we have observed that perinatal age is a critical period in the maturation of hormone receptors. In this period the presence of hormone induces the development of its specific receptors. The phenomenon is termed hormonal imprinting [4, 5, 6]. During its maturation the receptor is flexible and the presence of non-specific hormones capable of binding to it may alter its normal development Accordingly, even a single hormone injection in the perinatal period may alter the hormone-sensitivity of the target organ.

Allylestrenol

Thyroid-testis interrelationship during the development and sexual maturity of the rat.

The effects of thyroidectomy and treatment with thyroxine (T4) were studied in immature male rats to evaluate the role of the thyroid in the development of testicular functions. Thyroidectomy inhibited gametogenesis and development of the Leydig cell in these rats. However, the effects could be reversed by administration of 10 micrograms T4 (i.p.) daily for 30 days.

Animals

Insulin-like growth factor I in the developing and mature rat testis: immunohistochemical aspects.

The distribution of insulin-like growth factor I (IGF-I; somatomedin C) was mapped in testes of different aged rats by using immunohistochemical techniques. The antiserum used, K 624, has been demonstrated to be specific for human IGF-I, as defined by several criteria. Antibodies to the M1 subunit of ribonucleotide reductase, a key enzyme in DNA synthesis, were used to visualize meiotic and mitotic cells. Cytoplasmic IGF-I-like immunoreactivity as demonstrable during the first two postnatal weeks in spermatogenic cells, in Sertoli cells, and in Leydig cells. The IGF-I-like immunoreactivity decreased in the Sertoli and Leydig cells during the third and fourth postnatal weeks, and in adult rats, only spermatogenic cells showed IGF-I-like immunoreactivity. In mature rat testes, the spermatocytes were strongly immunoreactive. During puberty and adulthood, the spermatogonia expressed subunit M1 ribonucleotide reductase immunoreactivity, whereas no IGF-I-like immunoreactivity could be detected. No extracellular immunoreactivity was observed. We propose that IGF-I and/or IGF-I-like substances, possibly formed by primary spermatocytes, are likely to be involved in differentiation processes, but not in the initiation of cell proliferation in adult testes. The autocrine and/or paracrine action of IGF-I and/or IGF-I-like substances may thus have different action in developing testes than in adult testes. Our results do, however, not allow firm statements about whether IGF-I and related substances exert their actions on Sertoli cells or spermatogenic cells.

Aging

Acid phosphatases in the mouse testis: activity changes during development.

The histology and acid phosphatase activities of the developing testes in the mouse, from 4 days of age until maturity, were analyzed. The specific enzyme activity with p-nitrophenyl phosphate as substrate increased after 3 weeks of age and then reached a plateau. Cobalt and zinc markedly increased the specific activity after the third week. After fractionation the testicular homogenate revealed four acid phosphatases. Enzyme I maintained a high activity during the first 3 weeks but steadily declined thereafter. Enzyme II, present in all age groups, showed a moderate increase after the fourth week. Enzymes III and IV were low and declined further during the first 3 weeks with a subsequent increase. This occurred concomitantly with the appearance of spermatids and mature sperm cells. Changes in enzyme activities seem to reflect the alterations in cellular composition of the testis during the developmental process. Enzymes III and IV were probably associated with spermatids and sperm cells.

Acid Phosphatase

Expression profile of Ldh-a in the developing rat (Rattus norvegicus) testis suggests regulation at the translational level.

Expression of Ldh-a and Ldh-c mRNAs was examined in the rat testis. The mRNA levels of both Ldh-a and Ldh-c increase during testicular maturation. In the adult testis, Ldh-a mRNA is expressed maximally in primary spermatocytes. Comparison of the Ldh-a mRNA expression profile with its translation product suggests that this gene is translationally down-regulated during spermatogenesis.

Animals

Proliferation of Sertoli cells during development of the human testis assessed by stereological methods.

Sertoli cells were studied using stereological methods in testes obtained from five children who were stillborn, and 31 individuals between 3 months and 40 years of age, who had suffered from sudden, unexpected death. The mean nuclear volume of the Sertoli cells, the numerical density of Sertoli cells, and the total number of Sertoli cells per individual were determined by point- and profile-counting of 0.5 micron sections. The nuclear volume of Sertoli cells increased from a median of 120 microns3 (range 53-130) during the period of 3 months to 10 years to 210 microns3 (170-260) in adults (greater than 25 years). The numerical density of Sertoli cells decreased from a median of 1200 X 10(6)/cm3 (870-1400) during childhood (3 months to 10 years) to 140 X 10(6)/cm3 (110-260) in adults (greater than 25 years). The total number of Sertoli cells per individual increased significantly from a median of 260 X 10(6) (130-520) during the late foetal period to 1500 X 10(6) (850-2900) in individuals from 3 months to 10 years of age. A further increase was found during puberty as the number of Sertoli cells in adults (greater than 25 years) was 3700 X 10(6) (2500-5600). These results indicate that significant qualitative and quantitative changes in the population of Sertoli cells take place after birth.

Adolescent

Endocrine control of testicular somatic and premeiotic germ cell development in the immature testis of the primate Macaca mulatta.

Four groups(N = 3 per group) of juvenile rhesus monkeys (Macaca mulatta, 14-20 months old) received either vehicle or highly purified human follicle-stimulating hormone (FSH; 10 IU kg-1 day-1), human chorionic gonadotropin (hCG; 250 IU every alternate day) or both hormones for a period of 4 weeks. Testicular volume and weight increased more than twofold after single and more than sixfold after combined hormone treatment. Serum and intratesticular testosterone were at supraphysiological levels in hCG-treated animals and rose even more after combined treatment; a minor elevation of intratesticular testosterone was also observed after FSH treatment. Serum inhibin was elevated after hCG or FSH treatment and increased more than twofold during the first 3 weeks of combined treatment. Semiquantitative analysis of cell numbers showed a statistically non-significant increase in Sertoli cells and Ad- and Ap-spermatogonia after single hormone treatment. Combined treatment induced a further increase in the number of spermatogonia. Leydig cells were only encountered after hCG treatment; their number was more than threefold higher after combined treatment compared with hCG alone. Follicle-stimulating hormone stimulated Sertoli cell and Ap spermatogonia proliferation but did not induce morphological differentiation of Sertoli cells, peritubular cells or Leydig cells. Human CG treatment, however, induced Sertoli cell proliferation and morphological differentiation. It had effects on spermatogonial proliferation but induced differentiation of peritubular cells. Combined treatment initiated the greatest morphological and functional differentiation of Sertoli cells, peritubular cells, Leydig cells and spermatogonia. Flow cytometric analysis confirms an increase of mitotically active cells. The observations show that FSH and testosterone can induce Sertoli cell proliferation. Morphological differentiation of Sertoli cells may be mediated indirectly by environmental and paracrine stimuli released from peritubular cells, whose differentiation is androgen dependent. Leydig cells are stimulated mainly by hCG. Our present and previous data lead us to propose that FSH contributes to the final number and activity of Leydig cells, which secrete immunoreactive inhibin in response to hCG.(ABSTRACT TRUNCATED AT 400 WORDS)

Actins