Thyroid hormone affects the development of Sertoli cell function in the rat

1989 ◽  
Vol 123 (1) ◽  
pp. 105-111 ◽  
Author(s):  
S. Palmero ◽  
M. de Marchis ◽  
G. Gallo ◽  
E. Fugassa

ABSTRACT The relationship between thyroid activity and Sertoli cell function has been investigated in prepubertal rats. Male 28-day-old Wistar rats were used to prepare Sertoli cells by sequential enzyme digestion of the testes. Hypothyroidism, induced by oral administration of methimazole from the day of birth, was characterized by a severe retardation of body and testis growth and a net inhibition of the increase in Sertoli cell γ-glutamyl transpeptidase (GGT) activity as well as in androgen-binding protein (ABP) and lactate production, which normally occur during postnatal development of Sertoli cells. The functional parameters of Sertoli cells from hypothyroid 28-day-old rats approximated to those of cells from euthyroid 15-day-old animals. These results are consistent with the impairment of protein synthesis in Sertoli cells from hypothyroid rats compared with controls. Body and testis growth were improved and Sertoli cell functions were restored with 3,3′,5-tri-iodothyronine (T3) replacement therapy. An excess of T3 in the serum, induced by daily i.p. injections of T3 (100 μg/kg body wt) during the last week before the rats were killed, failed to induce changes in body and testis growth or in the activity of GGT and lactate dehydrogenase of Sertoli cells. Cells from hyperthyroid rats exhibited a specific decrease in ABP production. These results indicate that thyroid hormone is necessary for the postnatal maturation of Sertoli cell function and suggest a regulatory role of the hormone on gametogenic development in the prepubertal rat. Journal of Endocrinology (1989) 123, 105–111

1995 ◽  
Vol 145 (2) ◽  
pp. 355-362 ◽  
Author(s):  
S Palmero ◽  
M Prati ◽  
F Bolla ◽  
E Fugassa

Abstract The addition of physiological concentrations (1 nm) of tri-iodothyronine (T3) to the culture medium of Sertoli cells from prepubertal (8-day-old) rats stimulated both protein synthesis (+55%) and lactate (+50%) production, while it inhibited DNA synthesis (−30/35%) and aromatase activity (−45/50%); insignificant T3-dependent effects were observed in cultured Sertoli cells from midpubertal (28-day-old) rats. These data suggest an age-dependent role for thyroid hormone in promoting and maintaining Sertoli cell differentiation at puberty; moreover, the hormone is involved in the regulation of Sertoli cell proliferation. The present study validates the role of Sertoli cells as a specific target for T3 action at the testis level; it also demonstrates the existence of an early and critical direct influence of thyroid hormone on Sertoli cell proliferation and functional maturation. Journal of Endocrinology (1995) 145, 355–362


2002 ◽  
Vol 174 (2) ◽  
pp. 195-204 ◽  
Author(s):  
SB Meroni ◽  
MF Riera ◽  
EH Pellizzari ◽  
SB Cigorraga

The FSH molecular mechanism of action is best recognized for its stimulation of the adenylyl cyclase/cAMP pathway via activation of a G protein. Recently, links between cAMP, phosphatidylinositol 3-kinase (PI3K) and protein kinase B (PKB) signaling pathways in thyroid and granulosa cells have been observed. The aim of this study was to investigate the possible role of the PI3K/PKB pathway in FSH regulation of Sertoli cell function. Twenty-day-old rat Sertoli cell cultures were used. An increase in phosphorylated PKB (P-PKB) levels in response to FSH and dibutyryl-cAMP was observed. These increments in P-PKB levels were not observed in the presence of two PI3K inhibitors, wortmannin and Ly 294002. Inhibition of protein kinase A (PKA) by H89 did not decrease FSH stimulation of P-PKB levels. Taken together, these results indicate that FSH increases P-PKB levels in a PI3K-dependent and PKA-independent manner in rat Sertoli cells. In addition, wortmannin partially inhibited the ability of FSH to stimulate two well-known parameters of Sertoli cell function - transferrin secretion and lactate production - at doses equal to or lower than 0.1 microM. Related to lactate production, a decrease in FSH stimulation of lactate dehydrogenase activity and of basal and FSH-stimulated glucose uptake was observed in the presence of wortmannin. These metabolic changes were in most cases accompanied by changes in the levels of P-PKB. Altogether, these results suggest a meaningful role of the PI3K/PKB pathway in the mechanism of action of FSH in rat Sertoli cells.


1986 ◽  
Vol 111 (3) ◽  
pp. 411-418 ◽  
Author(s):  
G. Renier ◽  
J. Gaulin ◽  
W. Gibb ◽  
P. Simard ◽  
T. K. Leung ◽  
...  

Abstract. Several studies suggest a role of Sertoli cells in the control of Leydig cell steroidogenesis. In order to verify this hypothesis, we have developed a system for the purification of pig Sertoli cells. These cells were then characterized by their morphological appearance in light and electron microscopy, their ability to bind [125I]follicle stimulating hormone (FSH) and their functional capacity as evaluated by adenosine 3',5' monophosphate (cAMP) accumulation and lactate production when in primary culture under basal and FSH-stimulated conditions. Crude Sertoli cell suspensions from immature porcine testes were fractionated on discontinuous Percoll gradients (densities 1.025, 1.039, 1.055, 1.080 g/ml). Highly purified Sertoli cells were contained in the second band (d: 1.039) generated on the gradient. These cells demonstrated morphological and functional integrity as evidenced by binding specifically [125I] FSH and by responding to FSH stimulation (by an increased production of cAMP and lactate after 3 days in primary culture), but not to human chorionic gonadotrophin (hCG). This preparation represents a useful model for the study of Sertoli cell functions and their interation with Leydig cells in the regulation of testicular steroidogenesis.


2008 ◽  
Vol 14 (3) ◽  
pp. 225-235 ◽  
Author(s):  
Taiza Stumpp ◽  
Edna Freymuller ◽  
Sandra M. Miraglia

AbstractSertoli cells are very important to spermatogenesis homeostasis because they control germ cell proliferation, differentiation, and death. Damages to Sertoli cells cause germ cell death and affect fertility. Etoposide is a potent chemotherapeutic drug largely used against a variety of cancers. However, this drug also kills normal cells, especially those undergoing rapid proliferation. In the testis, etoposide acts predominantly on intermediate and type B spermatogonia. Etoposide was shown to permanently alter Sertoli cell function when administered to prepubertal rats. Based on this, we decided to investigate whether etoposide can affect Sertoli cell morphology. For this, 25-day-old rats were treated with etoposide during 8 consecutive days and killed at 32, 45, 64, 127, and 180 days old. Testes were fixed in Bouin's liquid or in a mixture of 2.5% glutaraldehyde and 2% formaldehyde for analysis under light and electron microscopes, respectively. Sertoli cells showed morphological alterations such as the presence of chromatin clumps close to the nuclear membrane, nucleus displacement, and cytoplasmic vacuolization. Some Sertoli cells also showed nuclear and cytoplasmic degenerative characteristics, suggesting that etoposide causes severe damages to Sertoli cell.


1994 ◽  
Vol 130 (3) ◽  
pp. 308-312 ◽  
Author(s):  
S Palmero ◽  
P Trucchi ◽  
M Prati ◽  
E Fugassa ◽  
A Lanni ◽  
...  

Palmero S, Trucchi P, Prati M, Fugassa E, Lanni A, Goglia F. Effect of thyroid status on the oxidative capacity of Sertoli cells isolated from immature rat testis. Eur J Endocrinol 1994;130:308–12. ISSN 0804–4643 Our previous studies indicate the Sertoli cell as a target for thyroid hormone action at testis level. In the present study we evaluated the effect of thyroid hormone on Sertoli cell oxidative capacity measured by specific cytochrome oxidase (COX) activity and intracellular adenosine triphosphate (ATP) content. Sertoli cells were isolated from 21-day-old rats. Hypothyroidism, induced from the day of birth by administration of 0.025% methimazole, was characterized by a severe delay of body and testis growth and resulted in a lower COX activity (−40%, p ≥ 0.01) and a lower ATP content (−35%, p ≥ 0.01) by isolated Sertoli cells. Administration of triiodothyronine (10 μg/100 g body wt on alternate days) to hypothryoid rats improved body and testis growth and restored both COX activity and ATP content. The presence of high-affinity, low-capacity binding sites for triiodothyronine in Sertoli cell mitochondria also was demonstrated. This study, unlike that carried out on the whole testis from adult rats, demonstrates that thyroid hormone affects the energy metabolism of Sertoli cells from midpubertal rat testes. Silvio Palmero, Istituto di Fisiologia Generale, Università di Genova, Corso Europa 26,1-16132 Genova, Italy


1998 ◽  
Vol 157 (2) ◽  
pp. 275-283 ◽  
Author(s):  
SB Meroni ◽  
DF Canepa ◽  
EH Pellizzari ◽  
HF Schteingart ◽  
SB Cigorraga

To study the role of extracellular nucleosides and nucleotides in the regulation of Sertoli cells, the effects of agonists which occupy A1 and P2 purinergic receptors on aromatase and gamma-glutamyl transpeptidase (gamma-GTP) activities and on transferrin secretion were tested. Sertoli cell treatment with purinergic agonists for a prolonged period of time (72 h) resulted in an increase in aromatase activity under basal conditions. In cultures stimulated with FSH, purinergic agonists counteracted the inhibitory effect on aromatase activity that long-term treatment with FSH promoted. The effects of prolonged treatments with purinergic agonists on the other two parameters of Sertoli cell function were less pronounced. Neither gamma-GTP activity nor transferrin secretion was modified under basal conditions. On the other hand, under conditions where cell differentiation was favored by FSH treatment, reductions in gamma-GTP activity and transferrin secretion were usually observed. The results obtained in dbcAMP-stimulated cultures suggested that A1 agonists exert their regulatory function at the level of cAMP formation while P2 agonists act at a more distal point. The fact that morphological changes induced by FSH were reversed by both types of agonists, while those induced by dbcAMP were only abrogated by P2 agonists, supports this hypothesis. In summary, these results demonstrate that purinergic agonists may be important in the regulation of Sertoli cell function.


2019 ◽  
Vol 63 (1) ◽  
pp. 161-166
Author(s):  
Marcin Gołyński ◽  
Michał Metyk ◽  
Piotr Szkodziak ◽  
Krzysztof Lutnicki ◽  
Grzegorz Kalisz ◽  
...  

Abstract Introduction: Thyroid hormones play a major role in the regulation of testicular maturation and growth and in the control of Sertoli and Leydig cell functions in adulthood. When naturally occurring, hypothyroidism causes male hypogonadotropic hypogonadism and Sertoli cell function disorders, but when iatrogenic and methimazole-induced its influence on the pituitary-testicular axis function with respect to Sertoli cells is poorly known. Material and Methods: Male adult Wistar rats (n = 14) were divided into two groups: E – taking methimazole orally for 60 days, and C – control animals. After 60 d, the concentrations in serum of testosterone, follicle-stimulating and luteinising hormones, and inhibins A and B were measured. Testicles were examined morphologically: the apoptotic Sertoli cell percentage (ASC%) and number of these cells functional per tubular mm2 (FSCN/Tmm2) were calculated. Results: In group E, inhibin A was higher while inhibin B was lower than in group C. ASC% was higher and FSCN/Tmm2 lower in group E than in group C. Conclusion: A specific modulation of Sertoli cell function in the course of methimazole-induced hypothyroidism leads to a simultaneous concentration increase in inhibin A and decrease in B. Inhibin A might share responsibility for pituitary-testicular axis dysfunction and hypogonadotropic hypogonadism in this model of hypothyroidism.


1987 ◽  
Vol 114 (3) ◽  
pp. 459-467 ◽  
Author(s):  
V. Papadopoulos ◽  
P. Kamtchouing ◽  
M. A. Drosdowsky ◽  
M. T. Hochereau de Reviers ◽  
S. Carreau

ABSTRACT Production of testosterone and oestradiol-17β by Leydig cells from adult rats was stimulated by LH or dibutyryl cyclic AMP (10 and 2·5-fold respectively). The addition of spent medium from normal, hemicastrated or γ-irradiated rat seminiferous tubule cultures, as well as from Sertoli cell cultures, to purified Leydig cells further enhanced both basal (44 and 53% for testosterone and oestradiol-17β respectively) and LH-stimulated (56 and 18%) steroid output. Simultaneously, a decrease (20–30%) in intracellular cyclic AMP levels was observed. This stimulating factor (or factors) secreted by the Sertoli cells is different from LHRH, is of proteinic nature and has a molecular weight ranging between 10 000 and 50 000; its synthesis is not controlled by FSH nor by testosterone. This factor(s) involved in rat Leydig cell steroidogenesis, at a step beyond the adenylate cyclase, does not require protein synthesis for testosterone formation whereas it does for oestradiol-17β production. It should be noted that a germ cell–Sertoli cell interaction modulates the synthesis of this factor(s). J. Endocr. (1987) 114, 459–467


Endocrinology ◽  
1993 ◽  
Vol 132 (3) ◽  
pp. 975-982 ◽  
Author(s):  
J P de Winter ◽  
H M Vanderstichele ◽  
M A Timmerman ◽  
L J Blok ◽  
A P Themmen ◽  
...  

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