Pituitary gonadotropin-releasing hormone receptors. Effects of castration, steroid replacement, and the role of gonadotropin-releasing hormone in modulating receptors in the rat.

Frager, Marc; Pieper, David R.; Tonetta, Sharon A.; Duncan, Joyce A.; Marshall, John C.

doi:10.1172/jci110075

Cited by 157 publications

(51 citation statements)

References 43 publications

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“…Although it is well known that gonadal steroid hormones regulate the serum levels and pituitary content of LH (6)(7)(8)(9)(10)(11)(12)(13), little is known about their regulation of the biosynthesis of the subunits of LH at the transcriptional and the posttranscriptional levels. The excess production of a-subunits over LHf-subunits (14,15) has suggested that the rate of LHfl-subunit synthesis determines the amount of intact LH produced (16)(17)(18)(19).…”

Section: Introductionmentioning

confidence: 99%

Regulation of rat luteinizing hormone subunit messenger ribonucleic acids by gonadal steroid hormones.

Gharib¹,

Bowers²,

Need³

et al. 1986

J. Clin. Invest.

129

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Little is known about the hormonal regulation of luteinizing hormone (LH) biosynthesis. We have studied the regulation of LH messenger RNA (mRNA) levels by gonadal-steroid hormones in the rat. In one set of experiments, male and female rats were surgically gonadectomized (GDX) and killed 1, 3, 7, 14, 22, and 31 d postoperatively. In another set of experiments, male and female rats were surgically GDX and were injected subcutaneously with testosterone propionate (500 Mug/100 g body wt per d) or 17,8-estradiol 3-benzoate (10 lg/100 g body wt per d), respectively, beginning 3 wk postoperatively. Levels of serum LH were determined by radioimmunoassay and levels of LH subunit mRNAs in single pituitary glands were determined by blot hybridization analysis using labeled synthetic oligodeoxyribonucleotide probes that correspond to portions of the coding regions of the rat a-and LHfl-subunit mRNAs. 4 wk after gonadectomy, serum LH levels rose nine-and 20-fold, while a-subunit mRNA levels rose six-and 10-fold, and LHIf-subunit levels rose seven-and 14-fold, compared with controls in males and females, respectively. In gonadal-steroid hormone-treated male and female GDX rats, serum LH levels fell to 8 and 36% of control values, while a-subunit mRNA levels declined to 22 and 19%, and LH-f-subunit mRNA levels declined to 6 and 10% of control values, 48 h after injections were initiated, in males and females, respectively. We conclude that gonadal-steroid hormones negatively regulate the levels of both subunit mRNAs in GDX rats in a pattern that parallels the changes in serum LH values. These data suggest that gonadal-steroid hormone regulation of LH biosynthesis occurs, at least in part, at the level of LH subunit mRNAs due to effects at the transcriptional and/or RNA stability levels.

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Section: Introductionmentioning

confidence: 99%

Regulation of rat luteinizing hormone subunit messenger ribonucleic acids by gonadal steroid hormones.

Gharib¹,

Bowers²,

Need³

et al. 1986

J. Clin. Invest.

129

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“…Gonadectomy in rats is invariably associated with a 2-3-fold rise in gonadotrophin-releasing hormone receptors coincident with the rise in serum gonadotrophins (Frager, Pieper, Tonetta, Duncan & Marshall, 1981 ;Clayton & Catt, 1981a;Conne, Scaglioni, Lang, Sizonenko & Aubert, 1982). These responses can be prevented by immunoneutralization with a specific GnRH antiserum (Frager et ai, 1981; Clayton, Popkin & Fraser, 1982) suggesting that increased endogenous GnRH is essential for the post-gonadectomy rise in pituitary GnRH receptors and serum gonadotrophins.…”

Section: Introductionmentioning

confidence: 99%

Role of GnRH in the regulation of pituitary GnRH receptors in female mice

Naik¹,

Young²,

Saade³

et al. 1985

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“…GnRH acts by an initial step of binding to a plasma membrane receptor (28,29), and a considerable body of evidence has shown that GnRH is the main regulator of its own receptor on the gonadotroph. Castration results in an increase in GnRH receptors (GnRH-R), and this effect can be abolished by hypothalamic lesions, administration of GnRH anti-sera, or replacement of testosterone (30)(31)(32)(33). These manipulations prevent the rise in GnRH after castration, and injections of GnRH given subcutaneously every 8 h increased GnRH-R in these animals (30,32).…”

Section: Introductionmentioning

confidence: 99%

“…Castration results in an increase in GnRH receptors (GnRH-R), and this effect can be abolished by hypothalamic lesions, administration of GnRH anti-sera, or replacement of testosterone (30)(31)(32)(33). These manipulations prevent the rise in GnRH after castration, and injections of GnRH given subcutaneously every 8 h increased GnRH-R in these animals (30,32). Low dose infusions of GnRH can also increase GnRH-R, whereas high dose infusions reduce receptor number (34).…”

Section: Introductionmentioning

confidence: 99%

Regulation of pituitary gonadotropin-releasing hormone receptors by pulsatile gonadotropin-releasing hormone injections in male rats. Modulation by testosterone.

Garcia¹,

Schiff²,

Marshall³

1984

J. Clin. Invest.

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Abstract. on the serum T concentration. With one T implant, increasing GnRH doses per pulse stimulated GnRH-R in a linear manner and the maximum receptor concentration (703±99 fmol/mg) was seen after the 250 ng GnRH dose. In the presence of two T implants, GnRH-R was maximal (705±45 fmol/mg) after the 25-ng dose and higher doses did not increase receptors above control values. With four T implants, GnRH doses of 5 ng induced a maximum response, 17-50 ng/pulse did not increase GnRH-R, but receptors were again increased by the 250-ng dose (633±86 fmol/mg).After 48 h of pulsatile GnRH administration there was no correlation between the number of GnRH-R and LH responses to GnRH. In rats with one or two T implants, LH responses were absent after all but the 250-ng doses. In contrast, LH responsiveness was not impaired in the presence of four implants. Thus, low dose GnRH pulses down-regulate LH secretion by an action at a post GnRH-R site, and this effect is regulated by testosterone. The results show that GnRH, given in a pulsatile manner, regulates its own receptor, and physiological increases in serum T produce a 50-fold increase in the sensitivity of GnRH-R stimulation by GnRH.

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Pituitary gonadotropin-releasing hormone receptors. Effects of castration, steroid replacement, and the role of gonadotropin-releasing hormone in modulating receptors in the rat.

Abstract: A B S T R A C T To study the role of gonadotropin-releasing hormone (GnRH)

Cited by 157 publications

References 43 publications

Regulation of rat luteinizing hormone subunit messenger ribonucleic acids by gonadal steroid hormones.

Regulation of rat luteinizing hormone subunit messenger ribonucleic acids by gonadal steroid hormones.

Role of GnRH in the regulation of pituitary GnRH receptors in female mice

Regulation of pituitary gonadotropin-releasing hormone receptors by pulsatile gonadotropin-releasing hormone injections in male rats. Modulation by testosterone.

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