Basal Testosterone Secretion and Response to Human Luteinizing, Follicle-Stimulating, and Growth Hormones in Culture of Cells Isolated from Testes of Infants and Children

Berensztein, Esperanza; Belgorosky, Alicia; Davila, Tatjana; Rivarola, Marco A.

doi:10.1203/00006450-199510000-00020

Cited by 12 publications

(9 citation statements)

References 30 publications

(38 reference statements)

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“…Certain authors propose that the fetal Leydig cell population is involved in this phenomenon [5]. This is supported by the observation that cells isolated from the postnatal human testis produce more testosterone and exhibit a more pronounced response to LH during the first 7 months than during the second and third year of life and by the pattern of fetal Leydig cells present [38]. Thus, based on available evidence at the present stage, the neonatal Leydig cell population seems to reach a peak in numbers several months after birth and continue functioning until the first signs of pubertal development appear.…”

Section: Postnatal Differentiation Of Human Leydig Cellssupporting

confidence: 50%

Origin, Development and Regulation of Human Leydig Cells

et al. 2010

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Sex steroids are crucial regulators of sexual differentiation and the proper development of secondary sex characteristics and patterns of sexual behavior. Since Leydig cells are the primary major producers of these steroid hormones, maintenance of the normal functions of these cells determines the reproductive capacity and fertility of males. The present minireview discusses recent findings concerning endocrine and paracrine regulation of the proliferation, differentiation and involution of human Leydig cells. The physiology and function of the two distinct fetal and adult populations of human Leydig cells are described, with particular focus on the paracrine environment that triggers their differentiation and functional maturation. The roles of established and more recently discovered paracrine regulators of this maturation, including insulin-like factor 3, platelet-derived growth factor-α, desert hedgehog, ghrelin and leptin are considered. A brief description of the origin, ontogenesis and functional markers of human fetal and adult Leydig cells is presented.

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Section: Postnatal Differentiation Of Human Leydig Cellssupporting

confidence: 50%

Origin, Development and Regulation of Human Leydig Cells

et al. 2010

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“…To study the prepubertal testicular period of development, in previous reports (4,5) we have divided our study subjects in age groups of different functional activity. This is in line with several reports indicating that childhood, and particularly infancy, are not quiescent periods of testicular development, both in the interstitial (6) and in the seminiferous cord compartments (7,8).…”

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confidence: 99%

Apoptosis and Proliferation of Human Testicular Somatic and Germ Cells during Prepuberty: High Rate of Testicular Growth in Newborns Mediated by Decreased Apoptosis

Berensztein

Sciara

Rivarola

et al. 2002

The Journal of Clinical Endocrinology &Amp; Metabolism

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Programmed cell death and proliferation are evolutionary conserved processes that play a major role during normal development and homeostasis. In the testis, during the fetal and newborn periods, they might determine final adult size and fertility potential. In the present study, we have measured the relative number of testicular cells in apoptosis and in active proliferation in the seminiferous cords and in the interstitium, at different age periods of prepubertal testicular development in humans. Testes from 44 prepubertal subjects without endocrine and metabolic abnormalities were collected at necropsy. They were divided in three age groups (Gr): Gr 1, newborn (1- to 21-d-old neonates), n = 18, mean (+/-SD) age 0.3 +/- 0.23 months; Gr 2, post natal activation (1- to 6-month-old infants), n = 13, mean age 3.93 +/- 1.90 months; and Gr 3, early childhood period (1- to <6-yr-old boys), n = 13, mean age 31.5 +/- 18.9 months. Apoptosis was detected in 5- microm tissue sections using a modified terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay and cell proliferation was assessed by Ki-67 immunohistochemistry. Evaluation of apoptosis was confirmed by estimation of active caspase-3. Mean (+/-SD) testicular weight was 0.38 +/- 0.20, 0.54 +/- 0.35, and 0.51 +/- 0.11 g in Gr 1, Gr 2, and Gr 3, respectively. In Gr 1, there was a significant positive correlation between age and testis weight (P = 0.02). Mean (+/-SD) germ cell apoptotic index, AI, (% of apoptotic cells out of total cell number) was 15.0 +/- 6.60, 27.0 +/- 8.80 and 33.4 +/- 11.4 in Gr 1, Gr 2, and Gr 3, respectively. In Sertoli cells, it was 6.60 +/- 4.07, 22.0 +/- 14.0 and 27.5 +/- 19.8, respectively. In interstitial cells, it was 10.2 +/- 6.38, 18.0 +/- 6.70 and 25.7 +/- 15.5, respectively. In the three types of cells, AI in Gr 1 was significantly lower than in Gr 2 or Gr 3 (P < 0.05). Mean (+/-SD) germ cell proliferation index, PI, was 18.6 +/- 13.0, 10.0 +/- 6.50 and 10.9 +/- 6.24% in Gr 1, Gr 2, and Gr 3, respectively. In Sertoli cells and in interstitial cells PI was similar in the three age groups. The PI/AI ratio was used to compare relative differences among age groups. The PI/AI ratio of germ cells, Sertoli cells and interstitial cells in Gr 1 was significantly higher than in Gr 2 or Gr 3 (P < 0.05). It is concluded that, in normal subjects, there is a vigorous growth of the testis during the newborn period with subsequent stabilization during the first years of prepuberty. This cell growth seems to be mainly mediated by decreased apoptosis. The factors that modulate apoptosis of testicular cells are not known, but it is remarkable that this change takes place before the testosterone peak of the post natal gonadal activation of the first trimester of life. These changes taking place during the newborn period might be important to define testicular function in adults.

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“…At this age, Sertoli cells might undergo active proliferation necessary to stimulate maturation of spermatogonia or to sustain spermatogenesis during sexual maturation at a later age. Sertoli cells might also participate in paracrine modulation of postnatal Leydig cell activation, as suggested by our previous finding of FSH stimulation of testosterone secretion in prepubertal testicular cells in culture (13).…”

Section: Discussionmentioning

confidence: 70%

“…Previously, we had found that basal testosterone secretion and the response to LH/hCG stimulation of human prepubertal testicular cells in culture varied according to the age of the subjects (13). Indeed, during the first semester of life testosterone secretion was higher than in 1-to 3-year-old subjects, probably reflecting the steroidogenic potential of the testis in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…We have previously used cultures of human prepubertal mixed testicular cells prepared from testes collected at necropsy (12) to study the age-related capacity of these cells to secrete testosterone and to respond to LH, FSH and growth hormone (GH) stimulation (13). The aim of the present study was to evaluate the age-related basal secretion of inhibin B by these prepubertal cells in culture, as well as their response to FSH, LH and GH stimulation in vitro.…”

Section: Introductionmentioning

confidence: 99%

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Secretion of inhibin B by human prepubertal testicular cells in culture

Berensztein

Saraco²,

Belgorosky³

et al. 2000

European Journal of Endocrinology

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Objective: Inhibin B is a secretory product of Sertoli cells of the human testis. It has been reported that serum levels of inhibin B in infant boys, peaking at 3 months of age, exceed levels in adult men. The aim of this study was to evaluate inhibin B secretion in primary prepubertal mixed testicular cell cultures, prepared from testes collected at necropsy. Design and Methods: Cell cultures were divided into three age groups on the basis of differences in testicular histology: group 1 (n ¼ 7), 1-to 10-day-old newborns, group 2 (n ¼ 7), 1-to 9-month-old infants, and group 3 (n ¼ 8), 12-to 84-month-old children. Cells were maintained in culture for 6 days, harvested and counted. In some samples, during the last 4 days, cells were stimulated with 10 ng/ml highly purified human (h) LH (n ¼ 9), 2 ng/ml recombinant human (rh) FSH (n ¼ 9) or 50 ng/ml rhGH (n ¼ 4). On day 6, the secretion of inhibin B and testosterone into the medium was estimated in triplicate. Inhibin B was determined by ELISA and testosterone by RIA. Results: Median (range) inhibin B secretion was 465 (225-1007), 275 (107-298), and 58 (15-184) pg/million cells.24 h in groups 1, 2 and 3 respectively. A logarithmic transformation of these values was performed to normalize data. Mean Ϯ S.D. of transformed inhibin B secretion in group 1 was significantly higher than in group 2 or 3 (P < 0:005) and the values for groups 1 and 2 were significantly higher than that for group 3 (P < 0:005). No significant correlation between testosterone and inhibin B secretion into the medium was found when the 22 culture samples were analyzed as a whole. Inhibin B secretion was significantly increased after stimulation with highly purified hLH, rhFSH and rhGH (P < 0:05) and a significant positive correlation between inhibin B and testosterone was found under both hLH and rhFSH stimulation. Conclusions: It is concluded that cells collected from newborns have the highest capacity to secrete inhibin B in vitro, and that this capacity decreases with age during the first years of life. Since no data are available on serum inhibin levels in newborns, it is possible that concentrations at 3 months of age do not represent a post-natal peak but a declining level of high newborn values. As expected, FSH stimulated inhibin B secretion in culture. LH stimulation was probably mediated by paracrine factors secreted by interstitial cells. Finally, our results add new evidence of the involvement of GH in testicular maturation.

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Basal Testosterone Secretion and Response to Human Luteinizing, Follicle-Stimulating, and Growth Hormones in Culture of Cells Isolated from Testes of Infants and Children

Cited by 12 publications

References 30 publications

Origin, Development and Regulation of Human Leydig Cells

Origin, Development and Regulation of Human Leydig Cells

Apoptosis and Proliferation of Human Testicular Somatic and Germ Cells during Prepuberty: High Rate of Testicular Growth in Newborns Mediated by Decreased Apoptosis

Secretion of inhibin B by human prepubertal testicular cells in culture

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