Gonadotropin and gonadal steroid release in response to a gonadotropin- releasing hormone agonist in G(q)α and G11α knockout mice

Dinesh Stanislaus, Jo Ann Janovick, Tae Ji, Thomas M. Wilkie, Stefan Offermanns, P. Michael Conn

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

In this study, we used mice lacking the G11α [G11 knockout (KO)] or G(q)α gent (G(q) KO) to examine LH release in response to a metabolically stable GnRH agonist (Buserelin). Mice homozygous for the absence of G11α and G(q)α appear to breed normally. Treatment of (5 wk old) female KO mice with the GnRH agonist Buserelin (2 μg/100 μl, sc) resulted in a rapid increase of serum LH levels (reaching 328 ± 58 pg/25 μl for G11 KO; 739 ± 95 pg/25 μl for G(q) KO) at 75 min. Similar treatment of the control strain, 129SvEvTacfBr for G11 KO or the heterozygous mice for G(q) KO, resulted in an increase in serum LH levels (428 ± 57 pg/25 μl for G11 KO; 884 ± 31 pg/25 μl for G(q) KO) at 75 min. Both G11 KO and G(q) KO male mice released LH in response to Buserelin (2 μg/100 μl of vehicle; 363 ± 53 pg/25 μl and 749 ± 50 pg/25 μl 1 h after treatment, respectively). These values were not significantly different from the control strain. In a long-term experiment, Buserelin was administered every 12 h, and LH release was assayed 1 h later. In female G11 KO mice and control strain, serum LH levels reached approximately 500 pg/25 μl within the first hour, then subsided to a steady level (~100 pg/25 μl) for 109 h. In male G11 KO mice and in control strain, elevated LH release lasted for 13 h; however, LH levels in the G11 KO male mice did not reach control levels for approximately 49 h. In a similar experimental protocol, the G(q) KO male mice released less LH (531 ± 95 pg/25 μl) after 13 h from the start of treatment than the heterozygous male mice (865 ± 57 pg/25 μl), hut the female KO mice released more LH (634 ± 56 pg/25 μl) after 1 h from the start of treatment than the heterozygous female mice (346 ± 63 pg/25 μl). However, after the initial LH flare, the LH levels in the heterozygous mice never reached the basal levels achieved by the KO mice. G11 KO mice were less sensitive to low doses (5 ng/per animal) of Buserelin than the respective control mice. Male G11 KO mice produced more testosterone than the control mice after I h of stimulation by 2 μg of Buserelin, whereas there was no significant difference in Buserelin stimulated testosterone levels between G(q) KO and heterozygous control mice. There was no significant difference in Buserelin stimulated estradiol production in the female G(q) KO mice compared with control groups of mice. However, female G11 KO mice produced less estradiol in response to Buserelin (2 μg) compared with control strain. Although there were differences in the dynamics of LH release and steroid production in response to Buserelin treatment compared with control groups of mice, the lack of complete abolition of these processes, such as stimulated LH release, and steroid production, suggests that these G proteins are either not absolutely required or are able to functionally compensate for each other.

Original languageEnglish (US)
Pages (from-to)2710-2717
Number of pages8
JournalEndocrinology
Volume139
Issue number6
DOIs
StatePublished - Jan 1 1998

ASJC Scopus subject areas

  • Endocrinology

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