Influence of thyroid hormone on androgen metabolism in peripuberal rat Sertoli cells

Panno, Maria Luisa; Beraldi, Eliana; Pezzi, Vincenzo; Salerno, M; G, De Luca; Lanzino, Marilena; Pera, Maria Le; Sisci, Diego; Prati, Mariangela; Palmero, S.; Bolla, Emilio; Fugassa, E; Andò, Sebastiano

doi:10.1677/joe.0.1400349

Cited by 37 publications

(28 citation statements)

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“…The quantum of oestradiol secretion by Leydig cells stimulated with T3 suggest that Leydig cell aromatase activity is more sensitive to thyroid hormones rather than LH. T3 inhibits the Sertoli cell aromatase activity and granulosa cell aromatase mRNA [41][42][43], whereas it stimulates the production of oestradiol in Leydig cells, suggesting cell specific differential role of thyroid hormones on testicular oestradiol production.…”

Section: Discussionmentioning

confidence: 97%

T3 Directly Stimulates Basal and Modulates LH Induced Testosterone and Oestradiol Production by Rat Leydig Cells in vitro.

2000

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Abstract.The effect of T3 on basal and LH mediated synthesis and secretion of testosterone and oestradiol by puberal rat Leydig cells was studied in vitro. Percoll gradient purified Leydig cells (1 x 103) were cultured for 48 hours at 34 ° C in a medium containing a range of 5-400 ng/mL concentration of T3 or ovine LH after 24 hours initial culture at 37 °C. T3 increased testosterone and oestradiol secretions in a dose dependent manner which reached the saturation point with 50 ng dose. While the minimum effective dose of T3 (25 ng) potentiated the stimulatory effect of the minimum effective dose of LH (25 ng) on testosterone secretion, it suppressed the effect of the saturation dose of LH (100 ng). Fifty ng T3 quelled the stimulatory effect of either dose of LH. Both doses of T3 increased oestradiol secretion, irrespective of the dose of LH. Addition of androstenedione (500 ng/mL) to the culture medium enhanced 25 ng T3 induced testosterone and oestradiol secretions. While androstenedione potentiated the stimulatory effect of T3 (25 ng) on LH (25 ng) induced testosterone and oestradiol secretions, it reversed the inhibitory effect of 50 ng T3 on LH mediated testosterone secretion which was accompanied by a decrease in oestradiol secretion. Puromycin (35 pg/mL) suppressed the stimulatory effect of T3 on basal and LH mediated testosterone and oestradiol production. Taken together, the present results indicate a direct stimulatory effects of T3 on basal production of testosterone and oestradiol by Leydig cells and its modulatory effect on LH mediated steroidogenic activity varies depending upon the intensity of LH stimuli.

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Section: Discussionmentioning

confidence: 97%

T3 Directly Stimulates Basal and Modulates LH Induced Testosterone and Oestradiol Production by Rat Leydig Cells in vitro.

2000

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“…This could very well have postponed the formation of Leydig cell progenitors from stem Leydig cells. Furthermore, several in vitro and in vivo studies have shown that the active thyroid hormone T 3 can directly influence Sertoli cell proliferation and function such as aromatase activity (34,48), androgen metabolism (35), and IGF-I production (33). The Sertoli cells in their turn have been reported to influence the formation of the adult-type Leydig cell population (reviewed in Ref.…”

Section: Discussionmentioning

confidence: 99%

Prenatal induced chronic dietary hypothyroidism delays but does not block adult-type Leydig cell development

Rijntjes

Swarts²,

Anand‐Ivell³

et al. 2009

American Journal of Physiology-Endocrinology and Metabolism

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Rijntjes E, Swarts HJ, Anand-Ivell R, Teerds KJ. Prenatal induced chronic dietary hypothyroidism delays but does not block adult-type Leydig cell development. Am J Physiol Endocrinol Metab 296: E305-E314, 2009. First published November 25, 2008 doi:10.1152/ajpendo.90750.2008.-Transient hypothyroidism induced by propyl-2-thiouracyl blocks postpartum Leydig cell development. In the present study, the effects of chronic hypothyroidism on the formation of this adult-type Leydig cell population were investigated, using a more physiological approach. Before mating, dams were put on a diet consisting of an iodide-poor feed supplemented with a low dose of perchlorate and, with their offspring, were kept on this diet until death. In the pups at day 12 postpartum, plasma thyroid-stimulating hormone levels were increased by 20-fold, whereas thyroxine and free tri-iodothyronine levels were severely depressed, confirming a hypothyroid condition. Adult-type progenitor Leydig cell formation and proliferation were reduced by 40 -60% on days 16 and 28 postpartum. This was followed by increased Leydig cell proliferation at later ages, suggesting a possible slower developmental onset of the adult-type Leydig cell population under hypothyroid conditions. Testosterone levels were increased 2-to 10-fold in the hypothyroid animals between days 21 and 42 postpartum compared with the age-matched controls. Combined with the decreased presence of 5␣-reductase, this implicates a lower production capacity of 5␣-reduced androgens. In 84-day-old rats, after correction for body weight-to-testis weight ratio, plasma insulin-like factor-3 levels were 35% lower in the hypothyroid animals, suggestive of a reduced Leydig cell population. This is confirmed by a 37% reduction in the Sertoli cell-to-Leydig cell ratio in hypothyroid rats. In conclusion, we show that dietary-induced hypothyroidism delays but, unlike propyl-2-thiouracyl, does not block the development of the adult-type Leydig cell population.

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“…The prolonged proliferation phase observed in immature Sertoli cells prepared from hypothyroid rats was associated with an increase in thyroid receptors (Palmero et al 1993), a dramatic enhancement of aromatase activity (Panno et al 1994) and increased estrogen-receptor content (Panno et al 1996b). Hormone replacement (with T 3 ) markedly shortened Sertoli cell replication (van Haaster et al 1993) and dramatically reduced both aromatase activity (Panno et al 1996b) and estrogen-receptor content (Panno et al 1996a).…”

Section: Introductionmentioning

confidence: 98%

Effects of tri-iodothyronine on alternative splicing events in the coding region of cytochrome P450 aromatase in immature rat Sertoli cells

Pezzi

Panno

Sirianni

et al. 2001

Journal of Endocrinology

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Transient postnatal hypothyroidism in male rats induces a prolonged proliferation of immature Sertoli cells. This change in Sertoli cell replication at young ages is coincident with enhanced and prolonged aromatase activity that leads to a marked increase in the conversion of androgens into estrogens. Both events are drastically inhibited by tri-iodothyronine (T 3 ) replacement either in vivo or in vitro. This study, after the immunolocalization of aromatase in cultured rat Sertoli cells, examined the effects elicited by T 3 on this enzyme, by simultaneously investigating three functional levels of aromatase: mRNA expression, protein content, and enzymatic activity. The immunolocalization of cytochrome P450 aromatase (P450 arom) was shown in the cytoplasm of cultured Sertoli cells from 15-and 21-day-old rats. Western blot analysis revealed an enhancement of aromatase protein content upon stimulation with N 6 ,2 -O-dibutyryladenosine-3 :5 -cyclic monophosphate ((Bu) 2 cAMP) that was clearly downregulated by T 3 . The presence of a functional P450 arom protein in purified Sertoli cells was confirmed by the measurement of [ H]androst-4-ene-3,17-dione. With 100 nM T3, a decrease in both P450 arom mRNA levels and aromatase activity was observed. The aromatase enzymatic activity was strongly stimulated by (Bu) 2 cAMP and markedly down-regulated by T 3 . In contrast, the strong increase in aromatase mRNA upon (Bu) 2 cAMP stimulation was apparently unaffected by T 3 administration. This paper shows how the identification of an altered transcript induced by T 3 coding for putative truncated and inactive aromatase protein might explain such a decrease in aromatase activity in T 3 -treated cells. On the basis of these results, it is concluded that at least two mechanisms could be involved in the down-regulatory effect of T 3 on aromatase activity in prepuberal Sertoli cells. The first mechanism is linked to a possible direct modulatory role for T 3 in the regulation of the aromatase promoter, whilst the second one is represented by the induction of altered transcripts coding for truncated and inactive aromatase proteins.

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Influence of thyroid hormone on androgen metabolism in peripuberal rat Sertoli cells

Cited by 37 publications

References 0 publications

T3 Directly Stimulates Basal and Modulates LH Induced Testosterone and Oestradiol Production by Rat Leydig Cells in vitro.

T3 Directly Stimulates Basal and Modulates LH Induced Testosterone and Oestradiol Production by Rat Leydig Cells in vitro.

Prenatal induced chronic dietary hypothyroidism delays but does not block adult-type Leydig cell development

Effects of tri-iodothyronine on alternative splicing events in the coding region of cytochrome P450 aromatase in immature rat Sertoli cells

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