Testicular Oxytocin Gene Expression in Seminiferous Tubules of Cattle and Transgenic Mice*

Ang, Hwee-Luan; Ungefroren, Hendrick; Bree, Freddy De; Foo, Ngee-Chih; Carter, David; Burbach, J. P. H.; Ivell, Richard; Murphy, David

doi:10.1210/endo-128-4-2110

Cited by 60 publications

(53 citation statements)

References 17 publications

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“…However, transfections of these cells with gene constructs encompassing up to 3.2 k b of the tentative bovine oxytocin promoter region have shown only a very low basal activity, but no transcriptional up-regulation of the transfected gene under culture conditions that lead to up-regulation of the chromosomal oxytocin gene (Walther, unpublished results). Possibly elements further away from the oxytocin coding region are necessary for up-regulation of transcription, as has been suggested from studies in transgenic mice (12,13). In the study presented here we have taken an alternative in vitro approach to analyse thc regulatory role of sequences from the 5' non-coding region of the bovine oxytocin gene.…”

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confidence: 99%

Mapping of the Bovine Oxytocin Gene Control Region: Identification of Binding Sites for Luteal Nuclear Proteins in the 5′ Non‐Coding Region of the Gene

Walther¹,

Wehrenberg²,

Brackmann³

et al. 1991

J Neuroendocrinology

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In view of the small number of hormone-producing cells, the factors regulating oxytocin gene expression in the classic site of synthesis, in the magnocellular neurons of the hypothalamus, have not yet been characterized. In the early bovine corpus luteurn there is a tissue-specific oxytocin expression involving many more cells. This tissue therefore was chosen as a experimental system to identify deoxyribonucleic acid elements and nuclear proteins involved in the regulation of oxytocin gene expression. 3.2 kb from the 5' non-coding region of the bovine oxytocin gene have been sequenced and subcloned fragments used as probes for gel retardation and footprinting experiments. Binding sites for luteal as well as more ubiquitous proteins were detected in the oxytocin promoter region and in an artiodactyl-specific dispersed repeated deoxyribonucleic acid element. A binding site in the promoter region with a superficial similarity to an estrogen-responsive element (-159 to -152) was shown not to bind this steroid hormone receptor but to bind two nuclear proteins alternatively. One is a luteal protein, the other a more general transcription factor belonging to the steroid hormone receptor superfamily and similar, if not identical to the COUP protein. This alternative binding of a tissue-and phase-specifically expressed protein or an ubiquitous factor to the same site in the oxytocin promoter suggests a role for these two proteins in the transient up-regulation and subsequent down-regulation of the oxytocin gene during the differentiation of the bovine corpus luteum.

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confidence: 99%

Mapping of the Bovine Oxytocin Gene Control Region: Identification of Binding Sites for Luteal Nuclear Proteins in the 5′ Non‐Coding Region of the Gene

Walther¹,

Wehrenberg²,

Brackmann³

et al. 1991

J Neuroendocrinology

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“…Oxytocin is synthesized in the hypothalamic paraventricular and supraoptic nuclei during late embryogenesis (7) and is released into the circulation via the posterior pituitary. Oxytocin is also synthesized in the corpus luteum (8,9), uterus (10,11), placenta (12), amnion (13), and testis (14,15) although the mouse testis does not appear to be a source of oxytocin (15). Whereas posterior pituitary-derived oxytocin appears to regulate milk ejection, production of oxytocin in the uterus and/or placenta is believed to function to initiate and maintain parturition (10)(11)(12)16).…”

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confidence: 99%

Oxytocin is required for nursing but is not essential for parturition or reproductive behavior.

Nishimori

Young

Guo

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

649

435

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Oxytocin, a neurohypophyseal hormone, has been traditionally considered essential for mammalian reproduction. In addition to uterine contractions during labor and milk ejection during nursing, oxytocin has been implicated in anterior pituitary function, paracrine effects in the testis and ovary, and the neural control of maternal and sexual behaviors. To determine the essential role(s) of oxytocin in mammalian reproductive function, mice deficient in oxytocin have been generated using embryonic stem cell technology. A deletion of exon 1 encoding the oxytocin peptide was generated in embryonic stem cells at a high frequency and was successfully transmitted in the germ line. Southern blot analysis of genomic DNA from homozygote offspring and in situ hybridization with an exonic probe 3' of the deletion failed to detect any oxytocin or neurophysin sequences, respectively, confirming that the mutation was a null mutation.

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“…The expression patterns seen with bovine VP (31) and OT (Ref. 30 and this report) transgenes in mice suggest that the cell type-specific expression of these genes is mediated by interactions between multiple enhancers and repressors located in both transcription units.…”

Section: Table IImentioning

confidence: 58%

“…Note that ␣-tubulin and glyceraldehyde-6-phosphate dehydrogenase RNAs are expressed at different levels in different tissues and that the relative pattern of expression observed is consistent between animals. The oligonucleotide probes specific for the rodent and bovine OT and VP RNAs have been described (30,31). Northern blot autoradiograms from salt loading experiments were subjected to quantitative analysis.…”

Section: Methodsmentioning

confidence: 99%

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Bovine Oxytocin Transgenes in Mice

Carter²,

Ang³

et al. 1995

Journal of Biological Chemistry

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To gain insights into the molecular mechanisms that restrict the expression of the oxytocin gene to anatomically defined groups of neurons in the hypothalamus, we generated transgenic mice bearing bovine oxytocin genomic fragments. Appropriate neuron-specific and physiological regulation was observed in mice bearing transgene bOT3.5, which consists of the oxytocin structural gene flanked by 0.6 kilobase pair (kbp) of upstream and 1.9 kbp of downstream sequences. bOT3.5 is expressed in oxytocin magnocellular neurons in the mouse supraoptic nucleus and paraventricular nucleus, but transgene RNAs are excluded from vasopressin neurons. Replacement of the drinking diet of the transgenic mice with 2% (w/v) NaCl for 7 days significantly increased the abundance of bovine oxytocin transcripts in the supraoptic nucleus, but not in the paraventricular nucleus, in parallel with the endogenous mouse oxytocin RNA. Surprisingly, mimicry of the endogenous oxytocin gene expression pattern was lost with larger transgenes. Addition of 0.7 kbp of contiguous downstream sequences (transgene bOT) or linkage to the bovine vasopressin gene (transgene VP-B/bOT3.5) repressed hypothalamic expression. No mice were derived bearing transgene bOT6.4, which consists of the oxytocin structural gene flanked by 3 kbp of upstream and 2.6 kbp of downstream sequences, suggesting that the presence of this DNA is detrimental to normal embryonic development. These data suggest that while bOT3.5 contains sufficient cis-acting sequences to mediate expression to particular subsets of hypothalamic neurons, the overall regulation of the oxytocin gene is governed by multiple interacting enhancers and repressors.Ever since pioneering studies demonstrated that the posterior pituitary contains activities that stimulate uterine contraction (1) and milk ejection (2), the oxytocin (OT) 1 system has been a favorite model for the study of the regulation and function of an identified class of central peptidergic neurons. OT is synthesized as a prepropeptide in the cell bodies of anatomically defined groups (nuclei) of hypothalamic magnocellular neurons. This precursor is subject to cleavage and other modifications as it is transported down the axon to terminals located in the posterior pituitary (3). The mature peptide products (the nonapeptide OT and a putative carrier molecule termed neurophysin) are stored until neural inputs governed by physiological stimuli elicit their release into the general circulation (4). Through an interaction with OT receptors located in the uterus and mammary gland, OT stimulates smooth muscle contraction, leading to parturition or milk ejection.The single-copy structural gene encoding the OT prepropeptide consists of three exons and encompasses Ͻ1 kbp (5). The OT gene is highly homologous at both the structural and sequence level to the gene encoding the related neuropeptide vasopressin (VP). In mammals, the two genes are separated by a short intergenic region of 11 kbp in the rat (5) and of 3 kbp in the mouse (6) and are transcribed to...

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Testicular Oxytocin Gene Expression in Seminiferous Tubules of Cattle and Transgenic Mice*

Cited by 60 publications

References 17 publications

Mapping of the Bovine Oxytocin Gene Control Region: Identification of Binding Sites for Luteal Nuclear Proteins in the 5′ Non‐Coding Region of the Gene

Mapping of the Bovine Oxytocin Gene Control Region: Identification of Binding Sites for Luteal Nuclear Proteins in the 5′ Non‐Coding Region of the Gene

Oxytocin is required for nursing but is not essential for parturition or reproductive behavior.

Bovine Oxytocin Transgenes in Mice

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