Gonadotropin-Releasing Hormone and Its Agonist Inhibit Testicular Luteinizing Hormone Receptor and Steroidogenesis in Immature and Adult Hypophysectomized Rats*

Bambino, Thomas; Schreiber, James R.; Hsueh, Aaron J. W.

doi:10.1210/endo-107-4-908

Cited by 143 publications

(38 citation statements)

References 25 publications

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“…Treatment with GnRH agonists in vivo and in vitro have demonstrated an inhibitory effect of GnRH on Leydig cell steroidogenesis in immature and adult hypophysectomized rats (Bambino et al 1980), and in decapitated rat fetuses (Habert 1992). In organotypic cultures of fetal testis, Habert et al (1991) have also shown that a GnRH agonist inhibited basal testosterone production between 17·5-18·5 dpc and 20·5 dpc, and LH-stimulated testosterone production thereafter.…”

Section: Discussionmentioning

confidence: 99%

Fetal expression of GnRH and GnRH receptor genes in rat testis and ovary

Botte

Chamagne²,

Carre³

et al. 1998

Journal of Endocrinology

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The identification of gonadal gonadotropin-releasing hormone receptors (GnRH-R) and evidence of direct inhibitory effects of GnRH agonists upon steroidogenesis in adult rat gonads, lend credence to a putative intragonadal role of a locally secreted GnRH or GnRH-like peptide. Using reverse transcription-polymerase chain reaction followed by Southern blot hybridization and sequencing, we identified, both in the ovary and in the testis of fetal and adult rats, a fully processed GnRH messenger RNA (mRNA), the sequence of which, in adult testis, was identical to that found in the hypothalamus. We also detected in the testis, but not in the ovary, a transcript containing the first intron.The ontogeny of GnRH and GnRH-R gene expression was studied in rat gonads from 14·5 to 21·5 days postcoitum (dpc), using dot blot hybridization of total RNA. During this period, the levels of cyclophilin mRNA normalized to total RNA remained unchanged. Thus, we used cyclophilin as an internal standard. GnRH mRNA was detected in the ovary at 18·5 dpc, four days later than in the testis, and similar levels were found in both sexes at birth. GnRH-R mRNA was present at 14·5 dpc in the testis and at 15·5 dpc in the ovary, with the levels at 21·5 dpc being 2·4 times higher in the testis than in the ovary. GnRH and GnRH-R mRNA levels increased in both sexes in late fetal development, but this increase appeared two days sooner in the ovary compared with the testis, thus supporting the hypothesis that expression of the GnRH and GnRH-R genes is regulated in a sexdependent manner during fetal development. In all cases, expression of GnRH and GnRH-R preceded gonadotropin receptors in the gonads and initiation of gonadotropin secretion by the pituitary.

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Section: Discussionmentioning

confidence: 99%

Fetal expression of GnRH and GnRH receptor genes in rat testis and ovary

Botte

Chamagne²,

Carre³

et al. 1998

Journal of Endocrinology

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“…In contrast, inhibitory effects of LHRH on Leydig cell testosterone secretion are demonstrable in vitro and in vivo, but only after 3 or more days' exposure to LHRH, and this inhibition is particularly marked in the presence of concomitant stimulation with large doses of gonadotrophin (e.g Bambino, Schreiber & Hsueh, 1980;Hsueh, Schreiber & Erickson, 1981; reviewed by Hsueh & Jones, 1981). Thus, if these actions accurately reflect those of 'testicular LHRH' then this factor may be versatile in its effects on Leydig cell steriodogenesis.…”

Section: Seminiferous Tubule-leydig Cell Interactionmentioning

confidence: 99%

Local Control of Testicular Function

Sharpe

1983

Exp Physiol

124

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This review has shown that local control of testicular function exists at three different levels. (1) Regulation of the entry of substances into the testis via the operation of selective barriers at the level of the capillary endothelium, myoid layer and Sertoli cell tight junctions, and by control of the rate of interstitial fluid formation which is the medium for transport into and within the testis. These mechanisms permit the creation of specific micro‐environments around the Leydig cells and outside of the seminiferous tubules as well as within the tubules, prerequisites for the local interaction and communication summarized below. (2) Regulation of spermatogenesis by co‐ordination of changes in hormone responsiveness and function of the Sertoli cells with the requirements of the associated germ cells, this varying according to the stage of the spermatogenic cycle. These changes involve regulation of germ cell multiplication, their differentiation and translocation from the basal to the adluminal compartment of the seminiferous tubule and their release into the lumen. (3) Interaction between the seminiferous tubules and the Leydig cells via various factors. The purpose of this interaction is not certain but in the prepubertal testis it probably co‐ordinates development of the tubules and Leydig cells, whilst in the adult testis it probably functions to regulate the steroidogenic responsiveness of the Leydig cells in accordance with the stage‐dependent requirements of the adjacent seminiferous tubules. Local control mechanisms within the testis therefore appear to co‐ordinate the function of the different cell types in the two testicular compartments and, as this is essential for normal function of the testis, the importance of local factors is self‐evident. In each of the three areas there is still only limited information as to the precise operation of the various mechanisms and even less is known about the identity of the co‐ordinating agents. But, as most of the available information derives only from the last three years, the gaps in our knowledge are to be expected and it is certain that the next few years will see major advances in this area. If the interpretation of the data offered in this review proves accurate then we are on the threshold of a revolution in our understanding of the control of testicular function, and of spermatogenesis in particular. This can only lead to improved methods for regulation of fertility in the male.

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“…GnRH is known to directly inhibit testosterone production by unknown mechanisms [2,3]. It also inhibits the proliferation of some tumor cell lines [4,5], suggesting that it is also involved in specific cellular functions other than hormone secretion.…”

mentioning

confidence: 99%

Stimulation of Annexin A5 Expression by Gonadotropin Releasing Hormone (GnRH) in the Leydig Cells of Rats

Yao

Kawaminami

2008

Journal of Reproduction and Development

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Abstract. The distribution and regulation of annexin A5 expression, a gonadotropin releasing hormone (GnRH) receptor regulated protein in gonadotropes and luteal cells, in the testes of rats were examined. Immunocytochemical staining revealed high levels of annexin A5 in the Leydig and endothelial cells and lower levels in the primary spermatocytes and sperm. Hemicastration significantly increased the annexin A5 content of the remaining testis within 24 h. Annexin A5 immunoreactivity was increased mainly in interstitial tissues including the peritubular cells, while some spermatocytes also showed higher intensity of annexin A5 in the remaining testis. Administration of hCG (50 IU) enhanced the testicular content of annexin A5 after 24 h. This treatment expanded the area of interstitial tissue in the testis and increased annexin A5 immunoreactivity, but the area of the of endothelial cells was unchanged. Similarly, human chorionic gonadotropin (hCG) enhanced annexin A5 expression in a primary culture of testis cells that consisted of mainly interstitial cells. Because GnRH stimulates the expression of annexin A5 in the gonadotropes and luteal cells, we examined the effect of GnRH on annexin A5 expression in the testes. We found that des-Gly10 [Pro9]-GnRH ethylamide (100 nM), a GnRH agonist, increased annexin A5 expression in cultured testis cells and that Cetrorelix (100 nM), a GnRH antagonist, inhibited the effect of hCG on annexin A5 expression. These results suggest that pituitary luteinizing hormone promotes annexin A5 synthesis in Leydig cells and that this effect could be mediated by local GnRH in the testis. Key words: Annexin A5, Gonadotropin releasing hormone (GnRH), Human chorionic gonadotropin (hCG), Leydig cell, Rat (J. Reprod. Dev. 54: [259][260][261][262][263][264] 2008) onadotropin releasing hormone (GnRH) is a hypothalamic decapeptide that is primarily responsible for humoral control of reproduction. GnRH is secreted by GnRH neurons at the median eminence of the hypothalamus and is transported by the pituitary portal system to the gonadotropes of the anterior pituitary gland. GnRH binds to a specific G protein-coupled receptor and stimulates gonadotropin secretion. GnRH and its receptor are also reported to be expressed in tissues outside of the hypothalamus and pituitary gland, including the testis [1].Although the physiological role of GnRH in reproduction is well established, the functions of extrahypothalamic GnRH remain unclear. GnRH is known to directly inhibit testosterone production by unknown mechanisms [2,3]. It also inhibits the proliferation of some tumor cell lines [4,5], suggesting that it is also involved in specific cellular functions other than hormone secretion. For example, GnRH receptors in granulosa cells are thought to participate in follicular atresia [6]. So, it is interesting to know how GnRH works in the testis.We previously demonstrated that expression of annexin A5 is specifically stimulated by GnRH in pituitary gonadotropes [7]. Annexin A5 is a member of the annexin...

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Gonadotropin-Releasing Hormone and Its Agonist Inhibit Testicular Luteinizing Hormone Receptor and Steroidogenesis in Immature and Adult Hypophysectomized Rats*

Cited by 143 publications

References 25 publications

Fetal expression of GnRH and GnRH receptor genes in rat testis and ovary

Fetal expression of GnRH and GnRH receptor genes in rat testis and ovary

Local Control of Testicular Function

Stimulation of Annexin A5 Expression by Gonadotropin Releasing Hormone (GnRH) in the Leydig Cells of Rats

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