The mouse inhibin α-subunit promoter directs SV40 T-antigen to Leydig cells in transgenic mice

Kananen, Kirsi; Markkula, Merja; El-Hefnawy, Talal; Zhang, Fuping; Paukku, Tommi; Su, Jyan-Gwo J.; Hsueh, Aaron J. W.; Huhtaniemi, Ilpo

doi:10.1016/0303-7207(96)03802-6

Cited by 61 publications

(38 citation statements)

References 46 publications

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“…As shown previously (Kananen et al, 1995(Kananen et al, , 1996a, these mice develop gonadal tumors originating from Leydig and granulosa cells, with 100% penetrance, at the age of 5-6 months. To find out whether the extragonadal tumors frequently found in these mice were primary or because of metastases of gonadal tumors, we gonadectomized neonatal mice (Kananen et al, 1996b).…”

Section: Introductionsupporting

confidence: 75%

“…Histologically, the testes of bLHb-CTP/Inha/Tag mice showed massive hemorrhagic and invasive tumors with mitotic figures originating from Leydig cells (Figure 2b), the cellular origin of which has been verified by us before (Kananen et al, 1996a) and was reconfirmed by 3b-HSD I-specific immunostaining ( Figure 3d). In contrast, no macroscopic tumors were present at 3 months in the single TG Inha/Tag mice.…”

Section: Gonadal Tumorigenesis In Double Tg Blhb-ctp/inha/ Tag Micementioning

confidence: 52%

“…We have previously shown that tumorigenesis in Inha/ Tag mice is gonadotropin dependent (Kananen et al, 1995(Kananen et al, , 1996a(Kananen et al, , b, 1997, but it has not been clear whether LH or FSH is mainly responsible for the tumorigenesis.…”

Section: Discussionmentioning

confidence: 99%

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High levels of luteinizing hormone analog stimulate gonadal and adrenal tumorigenesis in mice transgenic for the mouse inhibin-α-subunit promoter/Simian virus 40 T-antigen fusion gene

et al. 2003

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Transgenic (TG) mice expressing the Simian virus 40 T-antigen under the control of the murine inhibin-a promoter (Inha/Tag) develop granulosa and Leydig cell tumors at the age of 5-6 months, with 100% penetrance. When these mice are gonadectomized, they develop adrenocortical tumors. Suppression of gonadotropin secretion inhibits the tumorigenesis in the gonads of intact animals and in the adrenals after gonadectomy. To study further the role of luteinizing hormone (LH) in gonadal and adrenal tumorigenesis, a double TG mouse model was generated by crossing the Inha/Tag mice with mice producing constitutively elevated levels of LH (bLHb-CTP mice). Our results show that in double TG mice (bLHb-CTP/Inha/Tag), gonadal tumorigenesis starts earlier and progresses faster than in Inha/Tag mice. Both ovarian and testicular tumors were histologically comparable with the tumors found in Inha/Tag mice. In addition, adrenal tumorigenesis was found in intact double TG females, but not in Inha/Tag females. Inhibin-a and LH receptor (LHR) were highly expressed in tumorigenic gonadal tissues, and the elevated LH levels were shown to be associated with ectopic LHR and high inhibin-a expression in the female adrenals. We conclude that in the Inha/Tag tumor mouse model, elevated LH levels act as a tumor promoter, advancing gonadal and adrenal tumorigenesis.

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Section: Introductionsupporting

confidence: 75%

Section: Gonadal Tumorigenesis In Double Tg Blhb-ctp/inha/ Tag Micementioning

confidence: 52%

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High levels of luteinizing hormone analog stimulate gonadal and adrenal tumorigenesis in mice transgenic for the mouse inhibin-α-subunit promoter/Simian virus 40 T-antigen fusion gene

et al. 2003

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“…Attempts to detect cell specific expression of YHR and myc D556H LHR in the gonads by immunohistochemistry were unsuccessful. Although the inhibin α-subunit mRNA can be detected in Leydig cells of immature and adult rats (Roberts et al, 1989) and the inhibin α-subunit promoter can target transgene expression to mouse Leydig cells (Kananen et al, 1996) it also targets expression to Sertoli cells (Hsu et al, 1995). In the rat testis, the temporal expression of LHR and inhibin α-subunit protein appears to be similar as both can be detected in fetal Leydig cells as early as embryonic day 14 (Huhtaniemi, 1995;Majdic G et al, 1997;O'Shaughnessy et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Constitutively active luteinizing hormone receptors: Consequences of in vivo expression

Meehan¹,

Narayan²

2007

Molecular and Cellular Endocrinology

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Activating mutations in the luteinizing hormone receptor (LHR) gene are one of the most common mutations found in the gonadotropin receptor genes. Human males with these mutations exhibit precocious puberty while females do not have an obvious phenotype. To better understand the pathophysiology of premature LHR activation, transgenic mice have been generated with an activating mutation in LHR and a genetically engineered ligand-activated LHR. This review will summarize the major findings obtained with these two genetically modified mouse models and briefly discuss the similarities and differences between them and with the human phenotype.

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“…These mice develop malignant Leydig and granulosa cell tumors (both expressing LHRs) with 100% penetrance at the age of 5 months (Kananen et al 1995, Kananen et al 1996. Tumor cell lines immortalized from these tumors (Leydig and granulosa) produced high levels of progesterone, and the resulting high serum level of progesterone and reduced gonadotropins (Kananen et al 1996, Rahman andHuhtaniemi 2001) were used as a markers of endocrine consequences of the treatment.…”

Section: In Vivo Trials Of Hecate-cgβ Conjugatementioning

confidence: 99%

Use of hecate–chorionic gonadotropin β conjugate in therapy of lutenizing hormone receptor expressing gonadal somatic cell tumors

Rivero-Müller¹,

Vuorenoja²,

Tuominen³

et al. 2007

Molecular and Cellular Endocrinology

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The mouse inhibin α-subunit promoter directs SV40 T-antigen to Leydig cells in transgenic mice

Cited by 61 publications

References 46 publications

High levels of luteinizing hormone analog stimulate gonadal and adrenal tumorigenesis in mice transgenic for the mouse inhibin-α-subunit promoter/Simian virus 40 T-antigen fusion gene

High levels of luteinizing hormone analog stimulate gonadal and adrenal tumorigenesis in mice transgenic for the mouse inhibin-α-subunit promoter/Simian virus 40 T-antigen fusion gene

Constitutively active luteinizing hormone receptors: Consequences of in vivo expression

Use of hecate–chorionic gonadotropin β conjugate in therapy of lutenizing hormone receptor expressing gonadal somatic cell tumors

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