Decreased, LH Surge

Some sections of the KE description were adapted from AOPs 309.

Luteinizing hormone (LH), together with follicle-stimulating hormone (FSH,) is one of the glycoprotein hormones, called gonadotropins, that control gonadal functions interacting trough specific receptors.  LH and FSH are secreted from the anterior pituitary gland in response to GnRH and play a complementary role in follicle development and ovulation. In many species, LH receptor (LHR) is primarily expressed in reproductive organs and functions coordinately to control steroidogenesis and ovulation. LHR is expressed primarily in the theca and granulosa cells of preovulatory ovarian follicles. In ovarian theca cells, LH through interaction with LHR, stimulates the secretion of androgens that are transferred to granulosa cells to be converted to oestradiol (E2) by aromatase. In granulosa cells, FSH stimulates the development of ovarian follicles, while LH action is involved in follicle development and maturation. LH regulates the expression of a variety of genes essential for ovulation which convert from cholesterol to pregnenolone resulting the synthesis of progesterone.  In fish, the nuclear progesterone receptor, which is a member of the nuclear receptor transcription factor superfamily, has been suggested as an essential factor for LH-dependent ovulation. In conclusion, A deficiency in LH and FSH production or action (e.g., receptor activation) compromises gametogenesis and gonadal steroid production thereby reducing female fertility.

(see also KE129)

• Circulating concentrations of gonadotropins in humans and common mammalian models (e.g., rodents, many livestock species) can be directly measured using either commercial or custom immunoassays (e.g., enzyme-linked immunosorbent assays, radioimmunoassay, etc.).
• Similar immunoassay-based methods have been developed for quantifying gonadotropins in fish (e.g., (Govoroun et al., 1998; Amano et al., 2000; Kah et al., 1989; Prat et al., 1996)). However, at present, antibodies specific for distinguishing LH and FSH are only available for a limited number of species, primarily salmonids (Levavi-Sivan et al., 2010).
• Expression of mRNAs coding for luteinizing hormone beta subunit (LHb) and follicle-stimulating hormone beta subunit (FSHb) tend to fluctuate in parallel in repeat-spawning fish and plasma concentrations LH and FSH in tilapia were also shown to fluctuate in parallel (reviewed in (Levavi-Sivan et al., 2010)). Consequently, the two gonadotropins are treated non-specifically for the purposes of the current key event.
• For small fish species limited plasma volumes relative to the sensitivity of the available immunoassay methods may impose limits on the ability to measure this key event directly and reliably.

Pulsatile LH secretion

• urine LH ➔ immunoassay
• serum LH ➔a time-resolved immunofluorometric assay (TRIFMA) (Bang 2017)
• intermittent jugular vein or tail tip bleeding
• in vivo GCaMP imaging (McQuillan, et al., 2019)  
• LbT2 cells is the major homologous cell line available for the study of FSH and LH synthesis and secretion ➔ELISA is used.

In the context of AOP566, the taxonomic applicability is restricted to mammals. However, LH is also present in other species invertebrate species and fish and avian.

Bang AK, Nordkap L, Almstrup K, Priskorn L, Petersen JH, Rajpert-De Meyts E, Andersson AM, Juul A and Jørgensen N, 2017. Dynamic GnRH and hCG testing: establishment of new diagnostic reference levels. Eur J Endocrinol, 176:379-391. doi: 10.1530/eje-16-0912

McQuillan HJ, Han SY, Cheong I and Herbison AE, 2019. GnRH Pulse Generator Activity Across the Estrous Cycle of Female Mice. Endocrinology, 160:1480-1491. doi: 10.1210/en.2019-00193