STUDIES ON THE TESTICULAR-HYPOPHYSEAL FEED-BACK MECHANISM IN MAN

1964 ◽  
Vol 45 (4_Suppl) ◽  
pp. S99-S124 ◽  
Author(s):  
Svend G. Johnsen

ABSTRACT Quantitative measurements of the urinary excretion of gonadotrophins and androgen metabolites have been correlated with the functional condition of the germinal epithelium in various forms of male hypogonadism. Data on the influence of Leydig-cells, Sertoli-cells and the spermatogenetic stages on the gonadotrophin production are given. The finding of some, previously undescribed, lesions in spermatogenesis in certain clinical conditions is discussed. It is concluded that the testicular-hypophyseal feed-back mechanism in man depends on a very late stage in spermatogenesis. The suggestion is put forward that the cytoplasm which is split off from the spermatid immediately before liberation of the mature spermatozoon produces the hypophyseal inhibitor.

1971 ◽  
Vol 67 (4) ◽  
pp. 756-766 ◽  
Author(s):  
Svend G. Johnsen

ABSTRACT Urinary total hypophyseal gonadotrophin (HG) analyses in 56 healthy men and 282 patients with a great variety of forms of male hypogonadism showed that in some clinical conditions HG is decreased, in others increased while in some others the HG level is normal. It has been shown, however, that primary damage of the germinal epithelium per se causes an increase of the HG level. It is necessary, therefore, to take the functional state of the germinal epithelium into account when HG excretion is used as a parameter of function and responsiveness of the hypophysis. By the testicular biopsy score count method described by the author, a figure (mean score, MS) is obtained which expresses the spermatogenetic state. Analysis of 284 patients with primary testicular disorders established a correlation between the log gonadotrophin value (log HG) and MS. It was found that the HG level in the control group of apparently healthy men was considerably higher than that corresponding to perfect spermatogenesis. The question whether »ideal« men with perfect spermatogenesis or »average healthy« men should be used as controls in gonadotrophin assays is a dilemma. By using the regression equation between log HG and MS the influence of various spermatogenetic states on the HG level was eliminated by transforming, in each patient, the log HG value to the value corresponding to a fixed mean score of 1.0. These transformed log HG values were then evaluated in the various disorders. Decreased values were found in hypopituitarism, infantilism, eunuchoidism, adiposogenital dystrophy (in adults) and hypogonadism secondary to metabolic disease. In all other conditions, the HG level corresponded to the spermatogenetic state. No extra-tubular factors seem to influence the HG level and no case of primary overproduction of gonadotrophins was found. The value of transforming gonadotrophin values to a defined spermatogenetic state in clinical and experimental studies is discussed.


1985 ◽  
Vol 22 (6) ◽  
pp. 610-616 ◽  
Author(s):  
D. E. Corrier ◽  
H. H. Mollenhauer ◽  
D. E. Clark ◽  
M. F. Hare ◽  
M. H. Elissalde

Dietary cobalt (265 ppm Co) induced polycythemia and consistent degenerative and necrotic lesions in the seminiferous tubules of rats. Cyanosis and engorgement of testicular vasculature on day 35 and thereafter was followed on day 70 by degenerative and necrotic changes in the germinal epithelium and Sertoli cells. Spermatogonia, primary spermatocytes and round spermatids were markedly affected, while elongated spermatids, spermatozoa, and Sertoli cells were more resistant. Damaged tubules, often present side by side with normal tubules, contained multinucleated giant cells composed of degenerated and necrotic spermatocytes and/or spermatids, sloughed germinal and Sertoli cells, and calcified necrotic debris. Necrotic tubules were frequently collapsed and devoid of epithelium except for occasional spermatogonia and surviving Sertoli cells. Lesions were not observed in the Leydig cells, cauda epididymis or seminal vesicles.


Author(s):  
Shirley Siew ◽  
Philip Troen ◽  
Howard R. Nankin

Testicular biopsies were obtained from six young male subjects (age range 24-33) who complained of infertility and who had clinical evidence of oligospermia. This was confirmed on histological examination which showed a broad spectrum from profound hypospermatogenesis to relatively normal appearing germinal epithelium. Thickening of the tubular walls was noted in half of the cases and slight peritubular fibrosis in one. The Leydig cells were reported as normal or unremarkable.Transmission electron microscopy showed that the thickening of the supporting tissue of the germinal epithelium was caused more by an increase in the thickness of the layers of the lamina propria than of the tubular wall itself. The changes in the basement membrane of the tubular wall consisted mostly of a greater degree of infolding into the tubule and some reduplication which gave rise to a multilayered appearance.


Development ◽  
1991 ◽  
Vol 113 (1) ◽  
pp. 311-325 ◽  
Author(s):  
C.E. Patek ◽  
J.B. Kerr ◽  
R.G. Gosden ◽  
K.W. Jones ◽  
K. Hardy ◽  
...  

Adult intraspecific mouse chimaeras, derived by introducing male embryonal stem cells into unsexed host blastocysts, were examined to determine whether gonadal sex was correlated with the sex chromosome composition of particular cell lineages. The fertility of XX in equilibrium XY and XY in equilibrium XY male chimaeras was also compared. The distribution of XX and XY cells in 34 XX in equilibrium XY ovaries, testes and ovotestes was determined by in situ hybridisation using a Y-chromosome-specific probe. Both XX and XY cells were found in all gonadal somatic tissues but Sertoli cells were predominantly XY and granulosa cells predominantly XX. The sex chromosome composition of the tunica albuginea and testicular surface epithelium could not, in general, be fully resolved, owing to diminished hybridisation efficiency in these tissues, but the ovarian surface epithelium (which like the testicular surface epithelium derives from the coelomic epithelium) was predominantly XX. These findings show that the claim that Sertoli cells were exclusively XY, on which some previous models of gonadal sex determination were based, was incorrect, and indicate instead that in the mechanism of Sertoli cell determination there is a step in which XX cells can be recruited. However, it remains to be established whether the sex chromosome constitution of the coelomic epithelium lineage plays a causal role in gonadal sex determination. Male chimaeras with XX in equilibrium XY testes were either sterile or less fertile than chimaeras with testes composed entirely of XY cells. This impaired fertility was associated with the loss of XY germ cells in atrophic seminiferous tubules. Since this progressive lesion was correlated with a high proportion of XX Leydig cells, we suggest that XX Leydig cells are functionally defective, and unable to support spermatogenesis.


Endocrinology ◽  
2005 ◽  
Vol 146 (3) ◽  
pp. 1035-1042 ◽  
Author(s):  
Susan Y. Park ◽  
J. Larry Jameson

The embryonic gonad is undifferentiated in males and females until a critical stage when the sex chromosomes dictate its development as a testis or ovary. This binary developmental process provides a unique opportunity to delineate the molecular pathways that lead to distinctly different tissues. The testis comprises three main cell types: Sertoli cells, Leydig cells, and germ cells. The Sertoli cells and germ cells reside in seminiferous tubules where spermatogenesis occurs. The Leydig cells populate the interstitial compartment and produce testosterone. The ovary also comprises three main cell types: granulosa cells, theca cells, and oocytes. The oocytes are surrounded by granulosa and theca cells in follicles that grow and differentiate during characteristic reproductive cycles. In this review, we summarize the molecular pathways that regulate the distinct differentiation of these cell types in the developing testis and ovary. In particular, we focus on the transcription factors that initiate these cascades. Although most of the early insights into the sex determination pathway were based on human mutations, targeted mutagenesis in mouse models has revealed key roles for genes not anticipated to regulate gonadal development. Defining these molecular pathways provides the foundation for understanding this critical developmental event and provides new insight into the causes of gonadal dysgenesis.


PEDIATRICS ◽  
1961 ◽  
Vol 27 (4) ◽  
pp. 578-588
Author(s):  
Stanley Levin ◽  
Mordecai H. Gordon ◽  
Harold M. Nitowsky ◽  
Carmen Goldman ◽  
Paul di Sant'Agnese ◽  
...  

A bulb ergographic method for estimating muscle strength was modified to permit quantitative measurements. Studies in a group of 13 convalescent children without muscle disease established the reliability of the method for repeated observations. Forty-five patients with cystic fibrosis, whose clinical conditions appeared stable, were accepted in a double-blind study comparing the effect of tocopherol or a placebo on serum tocopherol, S-GOT, weight gain, subjective improvement, and muscle strength as measured by the ergograph. Measurements were made at the beginning of the study, and 2 and 6 months after beginning tocopheryl acetate (10 mg/kg/day) or placebo therapy. Although statistically significant increases in serum tocopherol, weight, muscle strength, and clinical improvement were found at 2 and 6 months after beginning of the study, there were no significant differences between the two groups, except in serum content of tocopherol. In the tocopherol treated group, serum tocopherol became normal (0.83 to 1.05 mg/100 ml), but remained low (0.20 to 0.33 mg/100 ml) in the placebo group. Although the present study did not demonstrate a clinical functional effect of tocopherol therapy in patients with cystic fibrosis, its administration is recommended because of previously reported biochemical and pathologic evidence of vitamin E deficiency in these subjects.


1996 ◽  
Vol 8 (7) ◽  
pp. 1075 ◽  
Author(s):  
K Seidl ◽  
A Buchberger ◽  
C Erck

The present study was designed to clarify the non-neurotrophic role for neurotrophins in mouse testis. By means of SI nuclease protection assay we could demonstrate that the gene coding for the low-affinity nerve growth factor (NGF) receptor p75NGFR is transiently expressed during germ cell development. Gene expression for p75NGFR was detected in late-meiotic spermatocytes and early spermatids and was found to be co-expressed with trkB and trkC, two tyrosine kinase receptors, commonly regarded as the high-affinity receptors for brain-derived neurotrophic factor and neurotrophin-3. Gene transcripts for the high-affinity NGF receptor trkA were found exclusively in non-germ cells. Isolated Leydig cells, peritubular myoid cells and Sertoli cells, but not germ cells, could be identified as potential testicular NGF sources. Non-germ cells respond after incubation for several days with a sharp induction in NGF synthesis, which is accompanied by a loss of phenotypic expression patterns. The fact that p75NGFR mRNA expression was induced in cultured Sertoli cells and peritubular myoid cells suggests an autocrine mode of NGF action in these cells. Induction of NGF synthesis in cultured Leydig cells could be prevented by the glucocorticoid dexamethasone. Results indicate different roles for the individual neurotrophins in distinct testicular compartments and suggest that these neurotrophins might support testicular functions by signalling between individual cell types in an autocrine and paracrine manner.


2017 ◽  
Vol 38 (4Supl1) ◽  
pp. 2551
Author(s):  
Juliana Stephany de Souza ◽  
Maria Carolina Villani Miguel ◽  
Marcos Antônio Maioli ◽  
Arthur Nelson Trali Neto ◽  
David Giraldo Arana ◽  
...  

The study of gonadal development improves the understanding of factors that can influence the reproductive development process. This study aims to characterize bovine fetal testicular development and the testosterone level in the Nellore breed. For the study, 162 bovine fetuses aged between 3 and 8 months were collected from Nellore cows at a local abattoir. The fetal age was estimated by DP=8.4+0.087L+5.46?L, where DP is the estimated pregnancy day and L represents fetal length. The fetal gonadal weight (g), width (cm), and thickness (cm) were measured. Thereafter, the gonads were submitted to classic histology processes in 3-µm-thick slices cut at 210 µm intervals. The Sertoli cells, Leydig cells, and germ cells were counted. Blood samples were collected from umbilical cords for testosterone levels. The data were analyzed using the Spearman correlation test followed by Principal Component Analysis and one-way ANOVA to compare the averages between months. The testicular weight and volume were found to have a positive correlation with the numbers of Sertoli cells (r = 0.84; p < 0.0001 and r = 0.92; p < 0.0001, respectively), Leydig cells (r = 0.80; p < 0.0001 and r = 0.90; p < 0.0001, respectively), and germ cells (r = 0.84; p < 0.0001 and r = 0.93; p < 0.0001, respectively) and to be negatively correlated with testosterone plasmatic concentration (r = -0.31; p = 0.0001 and r = -0.22; p = 0.006, respectively) during pregnancy. After the fifth month, the numbers of Sertoli cells, Leydig cells and germ cells differed (p < 0.0001) from the following gestational months. The highest testosterone concentration (p = 0.007) was observed in the fifth month of gestation and was followed by a concentration decrease in the seventh and eighth months. The increase in cell quantity was responsible for the increase in testicular weight and volume during fetal development. On the other hand, the testosterone concentration followed the increase in testicular weight and volume until the 7th month of gestation and regressed during the 8th and 9th months, in addition to the increase in cell number.


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