Postnatal Growth of Mouse Seminal Vesicle Is Dependent on 5α-Dihydrotestosterone*

Shima, Hiroki; Tsuji, Motomu; Young, Peter; Cunha, Gerald R.

doi:10.1210/endo-127-6-3222

Cited by 53 publications

(18 citation statements)

References 39 publications

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“…This result is consistent with the decreased testosterone levels seen in these animals (Fig. 2 C ) since SV tissue is responsive to T (Shima et al, 1990). Given that histological examination of WT, HET, and KO testes revealed no striking differences in either architecture or spermatogenesis (Fig.…”

Section: Resultssupporting

confidence: 90%

Hypothalamic Dysregulation and Infertility in Mice Lacking the Homeodomain Protein Six6

Larder

Clark²,

Miller³

et al. 2011

J. Neurosci.

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The hypothalamus, pituitary, and gonads coordinate to direct the development and regulation of reproductive function in mammals. Control of the hypothalamic–pituitary– gonadal axis is dependent on correct migration of gonadotropin-releasing hormone (GnRH) neurons from the nasal placode to the hypothalamus, followed by proper synthesis and pulsatile secretion of GnRH, functions absent in patients with hypogonadal hypogonadism. In this study, we identify sine oculis-related homeobox 6 (Six6) as a novel factor necessary for proper targeting of GnRH expression to the limited population of GnRH neurons within the adult mouse hypothalamus and demonstrate that it is required for proper reproductive function in both male and female mice. Female Six6-null mice exhibit a striking decrease in fertility, failing to progress through the estrous cycle normally, show any signs of successful ovulation, or produce litters. Although basal gonadotropin production in these mice is relatively normal, analysis of GnRH expression reveals a dramatic decrease in total GnRH neuron numbers. We show that expression of Six6 is dramatically increased during GnRH neuronal maturation and that overexpression of Six6 induces GnRH transcription in neuronal cells. Finally, we demonstrate that this induction in GnRH expression is mediated via binding of Six6 to evolutionarily conserved ATTA sites located within the GnRH proximal promoter. Together, these data indicate that Six6 plays an important role in the regulation of GnRH expression and hypothalamic control of fertility.

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Section: Resultssupporting

confidence: 90%

Hypothalamic Dysregulation and Infertility in Mice Lacking the Homeodomain Protein Six6

Larder

Clark²,

Miller³

et al. 2011

J. Neurosci.

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“…Each strip was cut into small fragments (Ϸ2-4 mm thick) and immediately placed in culture. A method similar to that developed in Dr. Gerald Cunha's laboratory at the University of California at San Francisco for organ culture of seminal vesicle and bulbourethral gland was used to culture fragments of bovine ovaries (Cooke et al, 1987;Shima et al, 1990;Alarid et al, 1994). Bovine ovarian fragments were cultured on 12-mm-diameter floating filters (0.4 µm Millicell-CM, Millipore, Bedford, MD) in 0.5 ml Dulbecco's Modified Eagle's Medium (DMEM)-Ham's F-12 medium (1:1, vol/vol) containing 0.1% bovine serum albumin (BSA, Sigma, St. Louis, MO), 0.1% albumax (Gibco) and 0.05 mg/ml L-ascorbic acid (Sigma) in a 16-mm diameter well of a four-well culture plate (Nunc plate, Applied Scientific, South San Francisco, CA).…”

Section: Bovine Ovary Fragment Organ Culturementioning

confidence: 99%

Kit ligand actions on ovarian stromal cells: Effects on theca cell recruitment and steroid production

2000

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Factors that control recruitment of theca cells from ovarian stromal‐interstitial cells are important for early follicle development in the ovary. During recruitment, theca cells organize into distinct layers around early developing follicles and establish essential cell–cell interactions with granulosa cells. Recruitment of theca cells from ovarian stromal stem cells is proposed to involve cellular proliferation, as well as induction of theca cell‐specific functional markers. Previously, the speculation was made that a granulosa cell‐derived “theca cell organizer” is involved in theca cell recruitment. Granulosa cells have been shown to produce kit‐ligand/stem cell factor (KL). KL is known to promote stem cell proliferation and differentiation in a number of tissues. Therefore, the hypothesis was tested in the current study that granulosa cell‐derived KL may help recruit theca cells from undifferentiated stromal stem cells during early follicle development. The actions of KL were examined using adult bovine ovarian fragment organ culture and isolated ovarian stromal‐interstitial cells. In organ culture KL significantly increased the number of theca cell layers around primary follicles. Experiments using purified stromal‐interstitial cell cultures showed that KL stimulated ovarian stromal cell proliferation in a dose‐dependent manner. Stromal cell differentiation into theca cells was analyzed by the induction of theca cell functional markers (i.e., androstenedione and progesterone production). Bovine ovarian stromal cells produced low levels of androstenedione (5–40 ng/μg DNA) and progesterone (5–30 ng/μg DNA) in vitro that were approximately 20‐fold lower than theca cells under similar conditions. Treatment with KL did not affect ovarian stromal cell androstenedione or progesterone production. Interestingly, hormones such as estrogen and hCG did stimulate stromal cell steroid production. The results in this study suggest that granulosa cell‐derived KL appears to promote the formation of theca cell layers around small (i.e., primary) ovarian follicles. KL directly stimulated ovarian stromal cell proliferation but alone did not induce functional differentiation (i.e., high steroid production). Therefore, KL is proposed to promote early follicle development by inducing proliferation and organization of stromal stem cells around small follicles. Observations suggest that KL may act as a granulosa‐derived “theca cell organizer” to promote stem cell recruitment of ovarian stromal cells in a manner similar to the way that KL promotes hematopoietic and lymphoid stem cells in bone marrow and the thymus. Mol. Reprod. Dev. 55:55–64, 2000. © 2000 Wiley‐Liss, Inc.

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“…Nevertheless, we propose that lower testosterone was unlikely to be their underlying cause of infertility, because the serum testosterone level in all three transgenic males were similar and T2 was fertile. The male accessory glands, which are sensitive to serum testosterone levels (35,36), still developed to appropriate sizes in our transgenic males. As a next step in delineating the functions of EGF in spermatogenesis, overexpression in specific cell types, for example in pachytene spermatocytes, will help to establish the autocrine/paracrine role of EGF in spermatogenesis.…”

Section: Infertility May Be Related To Low Serum Testosterone Level Imentioning

confidence: 99%

Overexpression of Epidermal Growth Factor Induced Hypospermatogenesis in Transgenic Mice

Wong¹,

Kwan²,

Mak³

et al. 2000

Journal of Biological Chemistry

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The in vivo role of epidermal growth factor (EGF) is not well defined even though its effects on culture cells were well studied. To understand the developmental, physiological, and pathological roles of EGF, we have generated transgenic mice widely expressing human EGF with the use of the ␤-actin promoter. EGF and transforming growth factor ␣ (TGF␣) bind with equal affinity to the EGF receptor, a transmembrane tyrosine kinase, to trigger various biological responses. EGF and TGF␣ signaling are implicated in the development of the reproductive system. EGF also plays a physiological role in reproduction. Removal of the salivary gland in rodents, which reduces circulating EGF, reduces spermatogenesis, which can be corrected by EGF replacement. Here we show that in our transgenic males, only few post-meiosis II gametes were found, and the mice were sterile. This resembles a common cause of infertility in humans. Furthermore, the transgenic males had reduced serum testosterone. Our findings contrast the previous report on transgenic mice overexpressing TGF␣ in testis, which showed normal spermatogenesis. These data suggest that EGF is the active ligand for EGF receptor reported in germ cells, and proper EGF expression is important for completion of spermatogenesis.

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Postnatal Growth of Mouse Seminal Vesicle Is Dependent on 5α-Dihydrotestosterone*

Cited by 53 publications

References 39 publications

Hypothalamic Dysregulation and Infertility in Mice Lacking the Homeodomain Protein Six6

Hypothalamic Dysregulation and Infertility in Mice Lacking the Homeodomain Protein Six6

Kit ligand actions on ovarian stromal cells: Effects on theca cell recruitment and steroid production

Overexpression of Epidermal Growth Factor Induced Hypospermatogenesis in Transgenic Mice

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