Effect of investigational kisspeptin/metastin analog, TAK-683, on luteinizing hormone secretion at different stages of the luteal phase in goats

Abstract

This study aimed to examine the response of luteinizing hormone (LH) secretion and ovarian steroid profile to TAK-683, an investigational metastin/kisspeptin analog, through treatment during different stages of the luteal phase in goats. Nine cycling Shiba goats (4.4 ± 2.3 years old) were assigned to early luteal phase (ELP, n = 4), mid-luteal phase (MLP, n = 4), and control (n = 5) groups. The ELP and MLP groups were administered 50 µg of TAK-683 intravenously on either day 5 or between days 7–14 after ovulation, respectively. The control group received vehicle between days 7–14 after ovulation. Blood samples were collected at 10-min (2–6 h), 2-h (6–24 h), and 24-h (24–96 h) intervals after treatment. Significant increases in plasma LH concentration were detected during the periods of 3 to 5 h and 2 to 5 h in the ELP and MLP groups, respectively. Estradiol concentrations continuously increased with the rise of basal LH secretion after TAK-683 treatment in two goats of the ELP group with a surge-like release of LH, but not in the goats without LH surge, i.e. the MLP and control group ones. Plasma progesterone concentration and the lengths of estrous cycle in all groups did not change significantly from the time before and after treatment. Present findings indicate that the responses of LH and ovarian steroids to treatment with TAK-683 depend on the stage of the luteal phase of the estrous cycle. We suggest that the stimulatory effects of TAK-683 on LH secretion are reduced in the process leading to the mid-luteal phase in cycling goats.

Effects of Kisspeptin-10 on Hypothalamic Neuropeptides and Neurotransmitters Involved in Appetite Control

“…Kisspeptin has also been proposed to act as a bridge between energy homeostasis and reproduction [14]. To this regard, kisspeptin and its analog TAK-683 have been reported to stimulate luteinizing hormone release in vivo [15,16]. Moreover, central, but not peripheral, injection of kisspeptin-10 was found to decrease food intake in overnight fasted mice [5].…”

An administration of TAK-683 at a minimally effective dose for luteinizing hormone stimulation under the absence of the ovary induces luteinizing hormone surge in ovary-intact goats

“…More recent studies have indicated that the potential of a bolus administration of TAK-683 to GnRH/LH secretion differs between the ovariectomized [ 5 , 7 ] and ovary-intact [ 8 , 9 ] goats. The secretory pattern of GnRH/LH after a single intravenous injection of 50 μg of TAK-683 was shown to be characterized by episodic increases of relatively small amplitude in orchidectomized [ 5 ] and ovariectomized goats [ 5 , 7 ].…”

Review: kisspeptin and reproduction in the pig

“…The timing of oestradiol changes associated with TAK683 injection depended upon the phase of oestrous cycle at the time of treatment, but ovulation was induced in five of five does and four of five does when TAK683 treatment was initiated in the follicular and luteal phase of the oestrous cycle, respectively. The magnitude of LH release induced by TAK683 was greater when does were treated in the follicular phase (Endo et al, 2015) than in the luteal phase (Endo et al, 2015;Rahayu et al, 2017).…”