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D J Tindall

Publications and source records attributed to D J Tindall.

At least 127 records · Page 7Linked to original sources
PubMed1978

Mechanisms for the testicular hypertrophy which follows hemicastration.

The hormonal and testicular effects of hemicastration have been examined using rodent models. When rats were hemicastrated at 5 days of age, significant testicular hypertrophy was noted within 5 days. Hypertrophy decreased as the age at hemicastration approached 20 days and did not occur in rats 45 days of age or older. The changes in testicular weight were associated with significant (P less than 0.001) increases in serum FSH values from 10-20 days, but no significant alterations in the intratesticular concentration of testosterone occurred. Hemicastration also caused significant hypertrophy in testes depleted of germ cells. This was reflected by a substantial increase in testicular protein and DNA when compared to intact controls at 10, 15, and 20 days of age; however, the concentration of protein/microgram DNA was increased only at 15 days. These data indicate that 1) changes in serum FSH and not intratesticular testosterone are associated with the testicular hypertrophy which follows unilateral castration of immature animals; 2, a significant proportion of the hypertrophy can be attributed to non-germinal cells, the Sertoli cell being the prime candidate;3) the increase in testicular weight is primarily the result of an increase in cell number.

Animals↗
PubMed1976

Biochemical actions of follice-stimulating hormone in the sertoli cell of the rat testis.

The sequenc of biochemical events associated with the action of follicle-stimulating hormone (FSH) in the testis has been investigated using a Sertoli cell-enriched testis model system. The Sertoli cell-encriched testis, created by irradiation of male rats in utero, is devoid of germinal elements but contains a normal complement of supportive Sertoli cells. Comparison of the Sertoli cell-enriched testis with normal testis, demonstrates that the two types of testes contain equal numbers of FSH specific receptors, judged by the binding of labeled hormone. In addition, FSH over a concentration range from 6 X 10(-11) to 6 X 10(-9)M will stimulate the production of adenosine 3',5' monophosphate (cAMP) in the Sertoli cell-enriched testis in a manner indistinguishable from that of the normal testis. Incubation of Sertoli cell enriched testis also results in the activation of soluble cAMP-dependent protein kinase. This response to FSH is dependent upon the age of the animal and disappears at about 32 days of age. While sensitivity to the hormone can still be detected in mature Sertoli cell-enriched animals by the addition of the phosphodiesterase inhibitor 1-methyl-3-isobutyl-xanthine, no detectable increase in phosphodiesterase activity is apparent after 30 days of age. Injection of FSH into Sertoli cell-enriched animals results in an increase in total testicular protein synthesis as well as in the production of the Sertoli cell-specific protein, androgen-binding protein within 30 minutes. Furthermore, while hypophysectomy of Sertoli cell-enriched animals result in a decline of the testicular concentration of androgen-binding protein, the injection of FSH will stimulate and maintain the levels of androgen-binding protein in such animals. These results demonstrate that the Sertoli cell-enriched testis is capable of carrying out the sequence of biochemical events previously described for FSH in the normal testis and therefore, suggest that the Sertoli cell is the primary target cell for FSH action.

Age Factors↗
PubMed1976

Concerning the hormonal regulation of androgen binding protein in rat testis.

Androgen binding protein (ABP) was measured in testis following an acute injection of FSH to ascertain whether this protein could serve as an endpoint marker of FSH action in the Sertoli cell. A single intravenous injection of oFSH (200 mug NIH-S-10) resulted in a rapid stimulation of ABP activity in testis of either 10- or 14-day old rats. Maximal increases were noted by 2 h in both cases (undetectable to 0.9, and 0.3 to 1.5 pmol ABP/mg protein in 10- and 14-day old rats, respectively) and by 4h ABP activity had again returned to control values. Although FSH failed to acutely stimulate ABP in 60-day-old rats, hypophysectomy of these animals resulted in a return of sensitivity within 3 days. The acute stimulation of ABP by FSH was also shown to be dependent upon both the route of hormone administration and the dose of FSH. Finally, the rapid decrease in ABP activity following FSH could be prevented by injection of a second dose of hormone. ABP activity was also increased by intratesticular injection of an analog of cyclic AMP, 8-bromo cAMP. This response was also dose-dependent and the time course of response was indistinguishable from that resulting following FSH. A test of nucleotide specificity revealed that any adenine nucleotide would stimulate ABP, whereas guanine compounds were ineffective. Peptide hormone specificity was next examined. It was determined that 200 mug of a variety of crude pituitary hormone preparations (LH, GH, PRL and ACTH) were stimulatory. However, when highly purified hormones were utilized, hFSH (LER-1577) did not increase testicular ABP whereas 1 mug of oLH (Papkoff) was maximally stimulatory. Further studies revealed that all compounds (including peptide hormones and nucleotides) which resulted in acute elevation of ABP activity also increased the intratesticular concentration of testosterone. Moreover, a single ip injection of testosterone produced a steroid specific stimulation of ABP which reached maximal levels within 1 h. These findings suggest that the acute regulation of ABP activity in the testis may be a result of the intratesticular concentration of testosterone and not due to a direct effect of FSH as had been previously hypothesized.

Adenine Nucleotides↗
PubMed1975

Androgen-binding proteins in rat epididymis: properties of a cytoplasmic receptor for androgen similar to the androgen receptor in ventral prostate and different from androgen-binding protein (ABP).

The cytoplasmic recptor (CR) in rat epididymal 105,000 g supernatant was separated from the androgen-binding protein (ABP) by gel electrophoresis following labeling with [1,2,6,7-3H]-testosterone in vivo. ABP disappeared from epididymal supernatants after castration of hypophysectomy, while CR remained unchanged. CR was evenly distributed between caput and cauda, while much more ABP was present in caput. Properties of CR in epididymis and prostate were similar and distinctly different from ABP. Binding to CR was destroyed by charcoal treatment (1 mg/mg protein) of supernatant for 0 degrees C for 6 h, heating at 50 degrees C for 30 min, or exposure to the sulfhydryl blocking reagent, p-chloromercuriphenylsulfonate (1mM) at 25 degrees C for 30 min, while binding to ABP was unaffected. The isoelectric pH of CR (5.8) was higher than that of ABP (4.6). Dissociation of radioactive 5alpha-dihydrotestosterone (DHT) from CR and nuclear receptors was extremely slow (half-time at 0 degrees C is greater than 2 days), while dissociation from ABP was rapid (half-time at 0 degrees C is similar to 6 min). Cyproterone acetate (250 mg/100 g body weight) inhibited binding to CR both in epididymis and ventral prostate but did not affect binding to ABP. Nuclear uptake was inhibited by cyproterone to the same extent as binding to CR, indicating that nuclear uptake and binding are dependent on CR and independent of ABP. The time-course of uptake and binding in epididymal supernatant and nuclear fractions was essentially the same 1 day after bilateral castration when both CR and ABP were present or 8 days after castration when CR alone was present. It is concluded that the cytoplasmic receptor for androgen in rat epididymis has properties very similar to the androgen receptor in ventral prostate but different from ABP.

Androstenedione↗
PubMed1975

Androgen binding protein as a biochemical marker of formation of the blood-testis barrier.

Androgen binding protein (ABP) was measured during postnatal development in normal and irradiated rats to determine whether development of a blood-testis barrier and formation of a continuous lumen from testis to epididymis is correlated with entry of ABP into the caput epididymis. ABP is found in normal testis as early as 14 days postnatally (0.2 pmol/mg), at which time no blood-testis barrier is observed by the peroxidase perfusion technique. Previous findings have shown a close correlation of blood-testis barrier development and lumen formation. Indeed, ABP is not detectable in the epididymis until 18-20 days of age (1.0 pmol/mg) at which time blood-testis barrier formation and lumen development is complete. Whole body irradiation (125 rads) of pregnant rats at 19-20 days of gestation produces male offspring with seminiferous tubules remarkably free of germinal epithelium and containing essentially only Sertoli cells. These Sertoli cell-enriched (SCE) testes produce normal amounts of ABP between 14 and 21 days postnatally. However, between 21 and 30 days of age the specific activity of ABP is significantly higher in the SCE tests (2.8 pmol/mg protein) than in normal testis (0.5 pmol/mg protein). In the SCE testis neither blood-testis barrier development nor lumen formation are complete until 30 days of age, at which time ABP is first detectable in epididymis of the irradiated rat. Thereafter there is a gradual decline of ABP in the SCE testis-and a dramatic increase in the epididymis. NIH-FSH-S-10 (200 mug/rat) injected SC into 14-day-old normal rats stimulated ABP in the testis from control levels of 0.15 pmol/mg to 1.46 pmol/mg within 4 h after injection. However, no ABP was detectable in the epididymis of either the control or the FSH-stimulated rats. These findings suggest that entry of ABP into caput epididymis is an index of blood-testis barrier formation and lumen development.

Androgens↗