Absence of gonadotropin-induced desensitization of testosterone production in the neonatal rat testis

It, Huhtaniemi; Dw, Warren; Apter, Dan; Kj, Catt

doi:10.1016/0303-7207(83)90100-4

Cited by 15 publications

(6 citation statements)

References 19 publications

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“…No clear increase in the P:T ratio after hCG treatment was observed as a sign of a steroidogenic lesion (desensitization) in the C 21 steroid side-chain cleavage step, which is a clear response of adult rat ovaries and testes to high-dose LH/hCG stimulation [48]. The absence of this response has previously been found in the neonatal testis [49]. Hence, the lack of steroidogenic desensitization in response to high-dose gonadotropin stimulation seems to be a common functional feature of both the neonatal ovary and testis.…”

Section: Discussionmentioning

confidence: 83%

Development of Luteinizing Hormone Action in the Perinatal Rat Ovary1

Sokka

Hämäläinen

Kaipia

et al. 1996

Biology of Reproduction

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The expression of LH receptor (LHR) mRNA was studied in fetal rat gonads using polymerase chain reaction multiplication of reverse-transcribed mRNA. A primer pair corresponding to the extracellular domain of the receptor revealed the expression of LHR mRNA in fetal ovaries and testes as early as embryonic Day 13.5, the earliest age studied. The localization of LHR mRNA was examined in the perinatal rat ovary using in situ hybridization with two antisense probes, one encoding the extracellular and the other encoding the transmembrane domains of LHR. At the age of 4 days, only the extracellular LHR probe gave specific signal over ovarian stromal and follicular cells, excluding the ova. Three days later, similar distribution of specific hybridization was observed with both probes. In the 10- and 30-day-old rat ovaries, clear expression of LHR mRNA was found to be with both probes in theca cells. Gonadotropin-stimulated production of cAMP was studied in cultures of dispersed perinatal rat ovarian cells. When 5-day-old ovarian cells were cultured for 3 days in vitro and then stimulated by either hCG (0.1 mg/L) or FSH (1 mg/L) for 6 h, cAMP production was enhanced only in cells stimulated by FSH. In a similar experiment with 7-day-old ovarian cells, cAMP production was stimulated by both FSH and hCG. Stimulation with hCG (0.1 mg/L) during the 3-day culture caused homologous desensitization of cAMP production, but stimulation with FSH (0.1 mg/L) had no such effect. The desensitization of the LHR was also investigated by treating neonatal rats in vivo with a high dose of hCG (600 IU/kg BW s.c. as a single injection on Day 7) or with a dosage of recombinant human (rec) FSH on Days 3-9 (0.3 IU s.c twice daily). Thereafter, at the age of 10 days, the ovaries were incubated either with recFSH (200 IU/L) or hCG (CR-121; 0.1 mg/L) for 1 h. Homologous desensitization of cAMP production by hCG was observed, but the FSH-mediated cAMP production was not affected. The hCG-induced steroidogenesis (progesterone and testosterone production) was not desensitized. In conclusion, these findings indicate that 1) the expression of the mRNA encoding the extracellular domain of LHR, i.e., truncated receptor, occurs in fetal rat gonads as early as embryonic Day 13.5; 2) the expression of the truncated LHR mRNA occurs uniformly in the differentiating ovarian cells before the appearance of the functional theca cell layer; 3) full-length LHR message appears in the developing ovary concomitantly with appearance of differentiated theca cells; 4) homologous desensitization of cAMP output by hCG, without steroidogenic desensitization, is present in perinatal rat ovaries; and 5) no FSH-evoked desensitization of cAMP production occurs in perinatal ovaries.

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Section: Discussionmentioning

confidence: 83%

Development of Luteinizing Hormone Action in the Perinatal Rat Ovary1

Sokka

Hämäläinen

Kaipia

et al. 1996

Biology of Reproduction

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“…This reduction is already apparent 2 days after operation in immature rats and appears between days 3 and 4 after hypophysectomy in the adult. The refractoriness of fetal Leydig cells to the loss of their differentiated function after removal of the hypo¬ physis can be linked with the previous observation that injection of high doses of human chorionic gonadotrophin (hCG) desensitized Leydig cells in the adult (Saez, Morera & Haour, 1979) but not in the neonate or the fetus (Huhtaniemi, Warren, Apter & Catt, 1983;Warren, Huhtaniemi, Dufau & Catt, 1987). Secondly, since it has been shown that decapi¬ tation reduces the cumulative volume of Leydig cells by around 40% for the periods considered here (Eguchi, Arishima, Nasu et al 1978), it seems very likely that the maximum steroidogenic activity of Leydig tissue, in relation to its volume, increases after decapitation.…”

Section: Discussionmentioning

confidence: 86%

Effect of decapitation and chronic in-vivo treatment with a gonadotrophin-releasing hormone agonist on testicular steroidogenesis in the rat fetus

Habert

1992

Journal of Endocrinology

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To study the effect of in-vivo gonadotrophin-releasing hormone (GnRH) treatment on testicular testosterone production during late fetal life in the rat, 18.5-, or 20.5-day-old fetuses were decapitated and injected with either long-acting microcapsules containing the GnRH agonist D-Trp-6-GnRH or vehicle only. Two days later, fetal and maternal plasma was collected and fetal testes were removed and incubated for 6 h in medium with either 100 ng LH/ml or without LH. The GnRH agonist concentrations in the plasma of GnRH-treated decapitated male fetuses were comparable in the two age-related groups (5 nmol/l). After treatment of the fetus with D-Trp-6-GnRH, the agonist was recovered in maternal plasma, showing that this peptide can cross the fetal-maternal barrier. In 22.5-day-old decapitated vehicle-treated male fetuses, the plasma testosterone level dropped to that observed in control female fetuses, and treatment of decapitated male fetuses with the GnRH agonist did not further reduce it. At both days 20.5 and 22.5, basal in-vitro testosterone secretion by testes from decapitated vehicle-treated fetuses was lower than secretion by testes from intact control fetuses from the same litter, but LH-stimulated secretion was similar in both groups. Both basal and LH-stimulated secretion by testes from GnRH-treated decapitated fetuses was lower than secretion by testes from vehicle-treated decapitated fetuses and larger reductions were measured on day 22.5 than on day 20.5 (-48 vs -18% for basal secretion, and -76 vs -40% for LH-stimulated secretion).(ABSTRACT TRUNCATED AT 250 WORDS)

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“…This feature of fetal Leydig cells may be an adaptation to maintain high circulating testosterone levels for normal differen¬ tiation of the male reproductive tract (31). Other characteristics which distinguish fetal from "adult" Leydig cells include the inability of high concen¬ trations of homologous hormone to down-regulate LH receptors in fetal Leydig cells (32) and to de¬ sensitize fetal Leydig cells (33).…”

Section: Discussionmentioning

confidence: 99%

Differential regulation of steroidogenic enzymes metabolizing testosterone or dihydrotestosterone by human chorionic gonadotropin in cultured rat neonatal interstitial cells

Murono

1990

Acta Endocrinologica

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The present studies examined the effects of hCG on steroidogenic enzyme activities involved in the metabolism of testosterone or dihydroststosterone in cultured rat neonatal interstitial cells. 5\g=a\-reductaseand 17\ g=b\ \ x =r eq-\ hydroxysteroid dehydrogenase activities, which are involved in the conversion of testosterone to dihydrotestosterone and androstenedione, respectively, were low in cultured neonatal interstitial cells, were unresponsive to hCG and declined to undetectable levels during 14 days of culture. However, \g=D\5-3\g=b\-hydroxysteroiddehydrogenase-isomerase activity, which is involved in the biosynthesis of testosterone, and 5\g=a\-androstane-3\g=a\-hydroxysteroid dehydrogenase and 5\g=a\-androstane-3\g=b\-hydroxysteroid dehydrogenase activities, which are involved in the conversion of dihydrotestosterone to 5\g=a\-androstan\x=req-\ 3\g=a\,17\g=b\-dioland 5\g=a\-androstan-3\g=b\,17\g=b\-diol,respectively, were maintained or increased by hCG during the same culture period. These results demonstrate that 5\g=a\-reductase and 17\g=b\-hydroxysteroiddehydrogenase activities do not play a significant role in regulating testosterone accumulation in fetal/neonatal Leydig cells, and they suggest that these cells are adapted to maintain high testosterone but low dihydrotestosterone levels. The present results demonstrate also that fetal/neonatal Leydig cells differ from immature or adult Leydig cells with respect to the sensitivity of 5\g=a\-reductase activity to LH/hCG. Fetal Leydig cells in the rat appear around day 15-16 of gestation and begin to secrete testoste¬ rone, which stabilizes the male reproductive tract and accessory sexual organs (1). Some studies sug¬ gest that their appearance and secretion of testoste¬ rone is regulated by LH from the fetal pituitary gland (2,3) which is elevated during this period of development (4). However, others suggest that this process is independent of external regulatory con¬ trol, and is genetically programmed to occur (5,6). Nevertheless, fetal or neonatal Leydig cells re¬ spond to exogenous LH/hCG by increased testoste¬ rone formation (7,8), and cultured fetal/neonatal Leydig cells retain sensitivity to LH/hCG or cAMP for two or more weeks in culture (9,10). Afterbirth, fetal Leydig cells regress and circulating testoste¬ rone levels decline (11,12). Starting around the second or third week following birth, a second ("adult") generation of Leydig cells appear (13). Leydig cells from immature rats (20-40 days of age) actively synthesize testosterone; however, very little androgen is secreted because high 5ot-reductase ac¬ tivity converts testosterone to dihydrotestosterone (DHT), 5ct-androstan-3a,17ß-diol (3ct-diol) and 5ct-androstan-3ß,17ß-diol (3ß-diol) (14-16). Testo¬ sterone becomes the primary androgen secreted by adult Leydig cells because of the selective decline in 5a-reductase activity (15). Thus, 5a-reductase ac¬ tivity plays a key role in regulating testosterone ac¬ cumulation and secretion by Leydig cells.Previous studies have demonstrated that...

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Absence of gonadotropin-induced desensitization of testosterone production in the neonatal rat testis

Cited by 15 publications

References 19 publications

Development of Luteinizing Hormone Action in the Perinatal Rat Ovary1

Development of Luteinizing Hormone Action in the Perinatal Rat Ovary1

Effect of decapitation and chronic in-vivo treatment with a gonadotrophin-releasing hormone agonist on testicular steroidogenesis in the rat fetus

Differential regulation of steroidogenic enzymes metabolizing testosterone or dihydrotestosterone by human chorionic gonadotropin in cultured rat neonatal interstitial cells

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