Zebrafish Gonadotropins and Their Receptors: I. Cloning and Characterization of Zebrafish Follicle-Stimulating Hormone and Luteinizing Hormone Receptors— Evidence for Their Distinct Functions in Follicle Development1

Abstract

In the present study, we cloned and characterized zebrafish FSH receptor (Fshr) and LH receptor (Lhr). Both fshr and lhr were abundantly expressed in the zebrafish gonads; however, they could also be detected in the kidney and liver, respectively. When overexpressed in mammalian cell lines together with a cAMP-responsive reporter gene, zebrafish Fshr responded to goldfish pituitary extract but not hCG, whereas Lhr could be activated by both. It was further demonstrated that Fshr was specific to bFSH, while Lhr could be stimulated by both bovine FSH and LH. Low level of fshr expression could be detected in the immature ovary, but the level steadily increased during vitellogenesis of the first cohort of developing follicles. In contrast, the expression of lhr could barely be detected in the immature ovary, but it became detectable at the beginning of vitellogenesis and steadily increased afterward with the peak level reached at the full-grown stage. At the follicle level, the expression of fshr was very weak in the follicles of primary growth stage but significantly increased with the follicles entering vitellogenesis. However, after reaching the maximal level in the midvitellogenic follicles, the level of fshr expression dropped slightly but significantly at the full-grown stage. In comparison, the expression of lhr obviously lagged behind that of fshr. Its expression became detectable only when the follicles started to accumulate yolk granules, but the level rose steadily afterward and reached the peak at the full-grown stage before oocyte maturation. These results suggest differential roles for Fshr and Lhr in zebrafish ovarian follicle development.

Transcriptional regulation of the FSH receptor: New perspectives

“…Once in circulation, hormonal activity is directed through specific cell surface receptors, whose expression ultimately determines the site of action of these hormones. In the case of FSH, its receptor is expressed only in a subpopulation of gonadal somatic cells, Sertoli cells of the testis and granulosa cells of the ovary (Camp et al, 1991;Heckert and Griswold, 1991;Kliesch et al, 1992;Bockers et al, 1994;Houde et al, 1994;Sites et al, 1994;Dankbar et al, 1995;Rannikki et al, 1995;Tisdall et al, 1995;Xu et al, 1995;Yuan et al, 1996;Oktay et al, 1997;Yamamura et al, 2001;Mattiske et al, 2002;Bluhm et al, 2004;Kwok et al, 2005). Therefore, as the basis for directing FSH biological action to Sertoli and granulosa cells, the mechanisms regulating expression of Fshr are key determinants of endocrine control of gamete production and fertility.…”

Inhibition of spawning in zebrafish (Danio rerio): Adverse outcome pathways of quinacrine and ethinylestradiol

“…Fish exposed to QUIN demonstrated an increase in ovarian levels of LHr at 09:00. It is possible that the mature follicles that are not ovulated and/or spawned are responsible for the increased levels of LHr observed at 09:00 as this follicle stage demonstrates the highest level of expression (Kwok et al, 2005). This possibility is supported by the histological data as the proportion of mature follicles present in the ovaries of fish exposed to QUIN was similar to the control group; however, fewer eggs were being spawned in the QUIN group.…”

“…Expression of LHr increases with follicle stage and the highest level of expression is seen in mature follicles (Kwok, et al, 2005). Fish exposed to QUIN demonstrated an increase in ovarian levels of LHr at 09:00.…”

“…No Change  *The surge of LH responsible for switching the steroidogenic pathway to the production of 17α, 20β-P is a defining event in the maturation, which is why LHr expression is categorized under maturation in the AOP, however it should be noted that LHr also plays a role in follicular recruitment, steroidogenesis and possibly ovulation (Kwok et al, 2005).…”

Examination of the Ability of Gonadal Sex Change in Primary Males of the Diandric Wrasses Halichoeres poecilopterus and Halichoeres tenuispinis: Estrogen Implantation Experiments

“…However, the binding specificities of fish GTH receptors appear to be less than what is generally observed in mammals. For example, in sea bass [53] and zebrafish [54], bovine FSH activated both FSH and LH receptors expressed in mammalian cell lines, while bovine LH only activated the LH receptor. If the induction of testicular tissue in the honeycomb grouper is dependent on FSH signaling, this may explain why bovine LH was ineffective in inducing sex change in the present study.…”