Effect of gonadotrophin-releasing hormone agonist-induced suppression of LH and FSH on follicle growth and corpus luteum function in the ewe

Abstract

Continuous infusion of a gonadotrophin-releasing hormone (GnRH) agonist (buserelin) by osmotic minipump from day 1 of the luteal phase in five Welsh ewes resulted in a sustained suppression of plasma concentrations of FSH which increased three- to eightfold within 2 days after the end of infusion 29 days later. Plasma concentrations of LH increased three- to eightfold over the first 5 days of infusion and then became basal and non-pulsatile until 1 day after the end of infusion. Duration of the luteal phase and plasma concentrations of progesterone were not significantly different in control and treated ewes. Pulses of LH in control ewes were followed by increases in concentrations of progesterone in samples collected at 10-min intervals for 7 h on days 10 and 14 of the luteal phase. However, progesterone was also released in a pulsatile manner in the absence of LH pulses in both control and GnRH agonist-treated ewes. After natural luteolysis, no ovulation or corpus luteum function occurred in treated ewes up to 15 days after the end of treatment on day 29, even though oestrus, indicating follicular development and oestrogen secretion, had occurred 8-11 days after treatment ended. After 30 days of infusion the ovaries of GnRH agonist-treated ewes contained no follicles greater than 2.5 mm in diameter. In follicles of 1-2 mm in diameter the basal and LH-stimulated production of oestradiol and testosterone in vitro were similar in both control and GnRH agonist-treated ewes, and a similar proportion of these follicles was oestrogenic (greater than 370 mol oestradiol per follicle) in GnRH agonist-treated and control ewes. These results show (1) that progesterone secretion by the corpus luteum of the ewe can be sustained in the presence of basal concentrations but absence of pulsatile secretion of LH, and progesterone is released in a pulsatile manner whether or not LH pulses are present, (2) that follicular development beyond 2.5 mm in diameter in the ewe is dependent upon adequate stimulation by both LH and FSH and (3) that the continuous infusion of GnRH agonist is a simple method for providing reproducible suppression of LH and FSH and follicular development in the ewe to allow the study of gonadotrophin action on the ovary in vivo.

Plasma Steroid Profiles Following Follicle-Stimulating Hormone or Equine Chorionic Gonadotropin Injection in Cows Chronically Treated with Gonadotropin-Releasing Hormone Agonist.

“…In the synthesis of estrogen, a unique cascade (the so-called two-cell two-gonadotropin mechanism) has been demonstrated in the ovary [5]. By contrast, in cows treated repeatedly with GnRH-A, the activity of pituitary LH to stimulate thecal androgen synthesis might be almost ceased as previously reported in the ewe [14]. Therefore, injected FSH could not stimulate E 2 production because of the lack of substrate for aromatization in granulosa cells, although it exhibited FSH-like activity in granulosa cells to stimulate follicular growth and irINH secretion.…”

“…However, a chronic treatment with GnRH or its agonists (GnRH-A) can lead to suppression of the reproductive function that includes pituitary gonadotropin secretion, ovarian follicular growth, steroidogenesis and ovulation [1,2,4,13,17,18]. Desensitization of pituitary gonadotropin secretion that induces suppression of follicle-stimulating hormone (FSH) secretion and inhibition of pulsatile release of luteinizing hormone (LH) has been reported as being a result of chronic administration with GnRH-A [14].…”

Induction of ovarian activity and ovulation in an induced ovulator, the maned wolf (Chrysocyon brachyurus), using GnRH agonist and recombinant LH

“…Specifically, although serum progesterone concentrations rise during estrus irrespective of implant sites, there are premature declines in steroid levels starting 1 to 4 weeks after hormone implant placement. In females exhibiting such declines, circulating deslorelin remains elevated (>100 pg/ mL) 20 days after implant administration, whereas that of individuals administered via vulva mucosa decreased to undetectable levels after 12 days [30]. Thus, prolonged release of the deslorelin into circulation may cause the downregulation of pituitary gonadotropins and premature luteal failure in female domestic dogs administered deslorelin subcutaneously [27,30].…”

“…In females exhibiting such declines, circulating deslorelin remains elevated (>100 pg/ mL) 20 days after implant administration, whereas that of individuals administered via vulva mucosa decreased to undetectable levels after 12 days [30]. Thus, prolonged release of the deslorelin into circulation may cause the downregulation of pituitary gonadotropins and premature luteal failure in female domestic dogs administered deslorelin subcutaneously [27,30]. Furthermore, it has been shown that GnRH and its agonists bind to specific receptors on the luteal cells that, in turn, suppress the production of progesterone in the rat [31].…”

Absence of regular pulsatile LH secretion during pre- and post-implantation periods in sheep

“…Indeed, the abolition of pulsatile LH release by chronic treatment of ewes with a GnRH agonist (17) or by treating ewes with a GnRH antagonist (18) had no effect on luteal function as assessed by changes in plasma concentrations of progesterone. These authors suggested that normal progesterone secretion by the sheep CL of the oestrous cycle can be maintained in the presence of basal concentrations of LH.…”