The Frequency of Gonadotropin-Releasing Hormone Secretion Regulates Expression of α and Luteinizing Hormone β-Subunit Messenger Ribonucleic Acids in Male Rats

Haisenleder, Daniel J.; Khoury, Sleman; Zmeili, S; Papavasiliou, Stathis; Ortolano, Girolamo A.; Dee, C.; Duncan, Joyce A.; Marshall, John C.

doi:10.1210/mend-1-11-834

Cited by 57 publications

(32 citation statements)

References 45 publications

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“…They are structurally similar, each consisting of an a subunit, common to all four hormones, and a unique, noncovalently associated ,B subunit (27). Expression of the glycoprotein hormone genes is controlled by a number of hormones, including sex steroids (21, 23, 26), thyroid hormone (30), hypothalamic hormones (15,16,25), and intracellular signals that act through cyclic AMP (cAMP)-dependent protein kinase A and protein kinase C (1, 6-8, 31). The genes are also under strict tissue-specific control.…”

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confidence: 99%

Expression of the glycoprotein hormone alpha-subunit gene in the placenta requires a functional cyclic AMP response element, whereas a different cis-acting element mediates pituitary-specific expression.

Bokar¹,

Keri²,

Farmerie³

et al. 1989

Mol. Cell. Biol.

117

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The single-copy gene encoding the a subunit of glycoprotein hormones is expressed in the pituitaries of all mammals and in the placentas of only primates and horses. We have systematically analyzed the promoterregulatory elements of the human and bovine a-subunit genes to elucidate the molecular mechanisms underlying their divergent patterns of tissue-specific expression. This analysis entailed the use of transient expression assays in a chorionic gonadotropin-secreting human choriocarcinoma cell line, protein-DNA binding assays, and expression of chimeric forms of human or bovine a subunit genes in transgenic mice. From the results, we conclude that placental expression of the human a-subunit gene requires a functional cyclic AMP response element (CRE) that is present as a tandem repeat in the promoter-regulatory region. In contrast, the promoter-regulatory region of the bovine a-subunit gene, as well as of the rat and mouse genes, was found to contain a single CRE homolog that differed from its human counterpart by a single nucleotide. This difference substantially reduced the binding affinity of the bovine CRE homolog for the nuclear protein that bound to the human a CRE and thereby rendered the bovine a-subunit promoter inactive in human choriocarcinoma cels. However, conversion of the bovine a CRE homolog to an authentic a CRE restored activity to the bovine a-subunit promoter in choriocarcinoma cells. Similarly, a human but not a bovine a transgene was expressed in placenta in transgenic mice. Thus, placenta-specific expression of the human a-subunit gene may be the consequence of the recent evolution of a functional CRE. Expression of the human a transgene in mouse placenta further suggests that evolution of placenta-specific trans-acting factors preceded the appearance of this element. Finally, in contrast to their divergent patterns of placental expression, both the human and bovine a-subunit transgenes were expressed in mouse pituitary, indicating differences in the composition of the enhancers required for pituitary-and placenta-specific expression.The glycoprotein hormone family consists of luteinizing hormone, follicle-stimulating hormone, thyroid-stimulating hormone, and chorionic gonadotropin. These hormones control diverse biological functions, including sexual function, pregnancy, and metabolism. They are structurally similar, each consisting of an a subunit, common to all four hormones, and a unique, noncovalently associated ,B subunit (27). Expression of the glycoprotein hormone genes is controlled by a number of hormones, including sex steroids (21, 23, 26), thyroid hormone (30), hypothalamic hormones (15,16,25), and intracellular signals that act through cyclic AMP (cAMP)-dependent protein kinase A and protein kinase C (1, 6-8, 31). The genes are also under strict tissue-specific control. All mammals synthesize luteinizing, follicle-stimulating, and thyroid-stimulating hormones in the pituitary, whereas synthesis of chorionic gonadotropin occurs in the placentas of only primates and horses (...

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confidence: 99%

Expression of the glycoprotein hormone alpha-subunit gene in the placenta requires a functional cyclic AMP response element, whereas a different cis-acting element mediates pituitary-specific expression.

Bokar¹,

Keri²,

Farmerie³

et al. 1989

Mol. Cell. Biol.

117

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“…Haisenleder el al. [14] used the same animal model to demonstrate that the frequency of the pulsatile GnRH stimulus regulates LHp and a-subunit mRNA levels. In ovariectomized (OVX), progesterone-replaced sheep, the frequency of adminis tration of GnRH regulated mRNA levels of all three gonadotro pin subunits, with LHp and FSHp responding similarly, and a-subunit being regulated differently [24], Nilson et al [28] …”

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confidence: 99%

Regulation of Follicle-Stimulating Hormone β and Common α-Subunit Messenger Ribonucleic Acid by Gonadotropin-Releasing Hormone and Estrogen in the Sheep Pituitary

et al. 1989

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The effect of gonadotropin-releasing hormone (GnRH) and/or estradiol (E₂) on pituitary messenger ribonucleic acid (mRNA) levels of luteinizing hormone β (LHβ), follicle-stimulating hormone β (FSHβ) and the common α-subunit were determined in anterior pituitary glands from ovariectomized (OVX) ewes. Hypothalamo-pituitary disconnected (HPD) ewes receiving appropriate hormonal treatment were used to assess the relative roles of GnRH and E₂ in directly regulating FSHβ and α-subunit mRNA levels. Levels of LHβ mRNA were increased in OVX animals compared with intact controls, and E₂ treatment of OVX animals significantly reduced mRNA levels of LHβ and FSHβ. HPD substantially reduced FSHβ and α-subunit mRNA levels. Treatment of OVX/HPD animals with pulses of GnRH (250 ng/2 h) for 1 week restored FSHβ and α-subunit mRNA to OVX levels. Combined GnRH and E₂ treatment significantly lowered FSHβ mRNA levels, but resulted in a rise in α-subunit mRNA levels. Treatment of OVX/HPD ewes with E₂ alone had no effect on FSHβ and α-subunit mRNA levels. These findings indicate that E₂ acts directly on the pituitary to negatively regulate FSHβ mRNA levels, and to positively regulate α-subunit mRNA levels in the presence of GnRH.

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“…demonstration that expression of a subunit and (3 LH messenger RNA is regulated by the frequency of GnRH stimulation [42].…”

Section: Lh In T Re Sp To L Hr Hmentioning

confidence: 99%

Time-Related Neuroendocrine Manifestations of Puberty: A Combined Clinical and Experimental Approach Extracted from the 4th Belgian Endocrine Society Lecture

Bourguignon¹

1988

Horm Res

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The neuroendocrine manifestations of puberty converge on changes in GnRH secretion. Their appraisal through the assay of GnRH-like material in 24-hour urine extracts shows an increased excretion of this material in the late prepubertal period. The most striking pubertal changes in GnRH secretion occur on a circadian and ultradian basis. In man, they can be evaluated only indirectly. The circadian variations in LH and FSH secretion characteristic of puberty may be observed in timed fractions of 24-hour urine with some delay when compared to the variations of plasma levels. Studies on the frequency of pulsatile LH secretion and during chronic intermittent administration of GnRH support the existence of an increased frequency of GnRH secretory episodes at puberty. LH response to synthetic GnRH is directly related to the frequency of stimulation by endogenous GnRH pulses and provides a very useful index of neuroendocrine maturation in patients with delayed or precocious puberty. A direct evaluation of pulsatile GnRH secretion is possible using the rat hypothalamus in vitro. In these experimental conditions, the frequency of pulsatile GnRH release increases during very early stages of sexual maturation in the male rat. GnRH itself and beta-endorphin are inhibitory regulators of GnRH secretion in vitro and may participate in the mechanisms restraining the pulse-generating machinery in the hypothalamus before puberty.

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The Frequency of Gonadotropin-Releasing Hormone Secretion Regulates Expression of α and Luteinizing Hormone β-Subunit Messenger Ribonucleic Acids in Male Rats

Cited by 57 publications

References 45 publications

Expression of the glycoprotein hormone alpha-subunit gene in the placenta requires a functional cyclic AMP response element, whereas a different cis-acting element mediates pituitary-specific expression.

Expression of the glycoprotein hormone alpha-subunit gene in the placenta requires a functional cyclic AMP response element, whereas a different cis-acting element mediates pituitary-specific expression.

Regulation of Follicle-Stimulating Hormone β and Common α-Subunit Messenger Ribonucleic Acid by Gonadotropin-Releasing Hormone and Estrogen in the Sheep Pituitary

Time-Related Neuroendocrine Manifestations of Puberty: A Combined Clinical and Experimental Approach Extracted from the 4th Belgian Endocrine Society Lecture

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