Age- and Sex-Specific Promoter Function of a 2-Kilobase 5′-Flanking Sequence of the Murine Luteinizing Hormone Receptor Gene in Transgenic Mice1

Hämäläinen, Tuula; Poutanen, Matti; Huhtaniemi, Ilpo

doi:10.1210/endo.140.11.7115

Cited by 25 publications

(1 citation statement)

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“…The expression persisted in the adults, confining to the cortical cell layers of the cerebrum, olfactory bulb, cerebellum, thalamus, posterior hippocampus, as well as the colliculi inferior and olivary nuclei of the brain stem. In comparison, Huhtaniemi and co-workers (49) observed recently that the mouse LHR promoter fragment of 2.1 kb directed lacZ reporter gene expression to adult brain areas that were only partially overlapping to the areas shown in the present study. These differences may be the result of the species differences or differences in the length and usage of the 5Ј-flanking sequences.…”

Section: Discussioncontrasting

confidence: 50%

Identification and Structural Characterization of the Neuronal Luteinizing Hormone Receptor Associated with Sensory Systems

Apaja

Harju

Aatsinki

et al. 2004

Journal of Biological Chemistry

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The luteinizing hormone receptor (LHR) is a G protein-coupled receptor involved in regulation of ovarian and testicular functions. Here we show that the receptor is present also in specific areas of the peripheral and central nervous system and may thus have a broader functional role than has been anticipated. Full-length LHR mRNA and two receptor protein species of M r 90,000 and 73,000, representing mature and precursor forms, respectively, were expressed in adult and developing rat nervous tissue, starting at fetal day 14.5. The receptor was capable of ligand binding because it was purified by ligand affinity chromatography, and human chorionic gonadotropin and LH were able to displace 125 I-labeled human chorionic gonadotropin binding to fetal head membranes in a dose-dependent manner. Finally, two 5-flanking sequences (ϳ 2 and 4 kb) of the rat LHR gene were shown to direct expression of the lacZ reporter to specific areas of the peripheral and central nervous system in fetal and adult transgenic mice, especially to structures associated with sensory, memory, reproductive behavior, and autonomic functions. Importantly, the transgene activity was confined to neurons and colocalized with the cytochrome P450 side chain cleavage enzyme. Taken together, these results indicate that the neuronal LHR is a functional protein, implicating a role in neuronal development and function, possibly by means of regulating synthesis of neurosteroids.

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Section: Discussioncontrasting

confidence: 50%

Identification and Structural Characterization of the Neuronal Luteinizing Hormone Receptor Associated with Sensory Systems

Apaja

Harju

Aatsinki

et al. 2004

Journal of Biological Chemistry

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Gonadotropin‐regulated testicular RNA helicase (GRTH/DDX25) gene: Cell‐specific expression and transcriptional regulation by androgen in transgenic mouse testis

Tsai‐Morris

Gutti

et al. 2010

J of Cellular Biochemistry

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Gonadotropin-regulated testicular RNA helicase is a multifunctional enzyme present in both Leydig and germ cells that is essential for the progress of spermatogenesis. GRTH gene expression is transcriptionally upregulated by human chorionic gonadotropin (hCG) via second messenger (cAMP) and androgen in Leydig cells. The regulatory region(s) in the GRTH gene that is/are required for its cell-specific expression in the testis and hCG/androgen dependent expression were investigated in transgenic mice carrying sequential deletions of 5' flanking sequences of the GRTH gene. GFP-reporter gene expression directed by the GRTH 5' flanking sequences extending to -3.6 kb was specifically located in Leydig cells and the 205 bp minimal promoter domain was sufficient for this cell-specific expression. The 1 kb (5' to the ATG codon) transgene-directed expression was markedly increased by in vivo hCG treatment. Administration of the androgen receptor inhibitor Flutamide blocked the basal and hCG stimulated GFP expression in Leydig cells. We conclude that the expression of GRTH in testicular cells is differentially regulated by its 5' flanking sequence and that the 1 kb fragment of GRTH gene contains sequences for androgen regulation of its expression in Leydig cells.

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Ovarian expression of human insulin‐like growth factor‐I in transgenic mice results in cyst formation

Dyck¹,

Parlow²,

Sénéchal³

et al. 2001

Molecular Reproduction Devel

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Insulin-like growth factor-I (IGF-I) has been implicated in a wide variety of physiological processes including ovarian function. To better understand the ovarian role of IGF-I, transgenic mice harbouring a human IGF-I cDNA (hIGF-I) under the control of the mouse LH receptor promoter were generated. Expression of the hIGF-I, determined by Northern blot, was found to occur in the gonad tissues of these transgenic mice. The hIGF-I protein was also detectable by radioimmunoassay in ovarian extracts as well as in the plasma. The fertility of mating transgenic females, as estimated by the number of implantation sites post-coitum, did not appear to be affected. However, transgenic females who failed to mate and produce offspring were found to possess polycystic ovaries. Evaluation of testosterone, estradiol, and LH levels revealed that transgenic animals had significantly elevated circulating levels of testosterone compared to their non-transgenic littermates, while LH levels in transgenic females were significantly lower. Yet, estradiol appeared to be unaffected. These results support the contention that the IGF system plays an important role in ovarian function and that an imbalance in this system may result in ovarian pathology.

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Age- and Sex-Specific Promoter Function of a 2-Kilobase 5′-Flanking Sequence of the Murine Luteinizing Hormone Receptor Gene in Transgenic Mice1

Cited by 25 publications

References 50 publications

Identification and Structural Characterization of the Neuronal Luteinizing Hormone Receptor Associated with Sensory Systems

Identification and Structural Characterization of the Neuronal Luteinizing Hormone Receptor Associated with Sensory Systems

Gonadotropin‐regulated testicular RNA helicase (GRTH/DDX25) gene: Cell‐specific expression and transcriptional regulation by androgen in transgenic mouse testis

Ovarian expression of human insulin‐like growth factor‐I in transgenic mice results in cyst formation

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