Assignment #3 : Function and Pathology

Dimeric Inhibin is produced in the male by the testis (Inhibin B only) and by the ovary in females (both A and B ). Also since inhibins are also produced by placenta and fetal membranes, it has been suggested that there is an involvement in physiological adaptation of pregnancy, at this time inhibin is produced by the fetoplacental unit (Inhibin A only) (McCullagh, R.,2003). All act in direct negative feedback on pituitary production of FSH (Follicle stimulating hormone). Inhibin B expression and secretion are positively correlated with Sertoli cell function, sperm number, and spermatogenic status. The sertoli cells in the testis promote spermatogenesis by increasing the local concentration of testerone, that is stumulated by FSH. Therefore, the sertoli cells produce Inhibin B that acts as a regulatory mechanism with a negative feedback on FSH at the pituitary. (Garem et al., 2002) Women have a different pattern of secretion throughout the menstrual cycle. Inhibin B is produced by the granulosa cells of the developing follicle in regulation that leads to follicular dominance in the menstrual cycle. Inhibin A is also produced by the follicle before ovulation and by the corpus luteum in the luteal phase. (Minami et al., 1995)

Figure 1. (A) Changes of serum inhibin A and inhibin B levels during the menstrual cycle. Redrawn from Groome et al. (1996). (B) Maternal serum inhibin A and pro-C levels during pregnancy and post-partum. According to Fowler et al. (1998).

There are several pathologies of inhibin; impending abortion, hydatidiform mole, and Down's syndrome.

Serum inhibin A measurement is used to predict poor outcome of pregnancy. It acts as a marker of placental dysfunction and damage both in the presence and prior to the onset of the clinical symptoms of recurrent miscarriage. Due to this the inhibin family act as markers of early pregnancy viability. Low levels and a very rapid decline of inhibin A occur in non-viable clinical pregnancies with embryonic failure, therefore patients who have subsequent miscarriage have inhibin A concentrations that are lower than patients who had a live birth (Muttukrishna et al., 2002).

Hydatidiform mole is a disease of the trophoblastic proliferation. This rare mass of growth mimic's pregnancy, it causes human chorionic gondotropin (HCG) levels to increase, therefore, producing a false positive reading on a pregnancy test (Wikipedia, 2007). Inhibin A levels are higher in molar pregnancy without any considerable overlap with normal pregnancy values at the same stage of pregnancy (Florio et al., 2002), this suggests that inhibin A plays a role in measurement in diagnosing molar pregnancies. Also, after molar removal, inhibin A declines considerably to values similar to those measured in non-pregnant women, whereas hCG levels decrease but remain far higher than in non-pregnant women.This suggests that inhibin A is more sensitive than hCG in identifying patients with spontaneous remission after molar evacuation(Florio et al., 2002).

Down's syndrome is a genetic disorder that is caused by the presence of all or part of an extra 21st chromosome (Wikipedia,2007). High maternal serum inhibin A levels are associated with Down's syndrome. Due to this fact, inhibin A levels can be used as part of a multiple prenatal screening marker, because it is not sensitive enough to be used alone (Wenstrom et al., 1999). Also when inhibin subunit is over expressed in second trimester placental tissue of pregnancy this is a indicator of fetal Down's syndrome (Lambert-Messerlian et al., 1998). The conclusion then can be made that increased subunit expression is one of the mechanisms leading to increased levels of inhibin A in serum.

References:

Down syndrome. (2007, March 12). In Wikipedia, The Free Encyclopedia. Retrieved 16:55, March 12, 2007, from http://en.wikipedia.org/w/index.php?title=Down_syndrome&oldid=114544712

Florio P, Severi FM, Cobellis L, Danero S, Bome A, Luisi S and Petraglia F (2002) Serum activin A and inhibin A. New clinical markers for hydatidiform mole. Cancer 94, 2618–2622.[CrossRef][ISI][Medline]

Fowler PA, Evans TW, Groome NP, Templeton A and Knight PG (1998) A longitudinal study of maternal serum inhibin A, inhibin B, activin A, pro-C and follistatin during pregnancy. Hum Reprod 12, 3530–3536.

Garem YF, Arini AF, Beheiry AH, Zeid SA and Comhaire FH (2002) Possible relationship between seminal plasma inhibin B and spermatogenesis in patients with azoospermia. J Androl 23, 825–829.

Hydatidiform mole. (2007, February 19). In Wikipedia, The Free Encyclopedia. Retrieved 14:43, March 12, 2007, from http://en.wikipedia.org/w/index.php?title=Hydatidiform_mole&oldid=109414694

Lambert-Messerlian GM, Luisi S, Florio P, Mazza V, Canick JA and Petraglia F (1998) Second trimester levels of maternal serum total activin A and placental inhibin/activin and ßA subunit messenger ribonucleic acids in Down syndrome pregnancy. Eur J Endocrinol 138, 425–429.[Abstract]

McCullagh, R. (2003). Inhibin. Inhibin Fertility and Reproduction Function. Retrieved March 12, 2007 from http://www.inhibin.com/Home/Static.aspx?PageID=0

Minami S, Yamoto M and Nakano R (1995) Sources of inhibin in early pregnancy. Early Pregn 1, 62–66.

Muttukrishna S, Jauniaux E, Greenwold N, McGarrigle H, Jivraj S, Carter S, Elgaddal S, Groome N and Regan L (2002) Circulating levels of inhibin A, activin A and follistatin in missed and recurrent miscarriages. Hum Reprod 17, 3072–3078.

Wenstrom KD, Owen J, Chu DC and Boots L (1999) Prospetic evaluation of free ß-subunit of human chorionic gonadotropin and dimeric inhibin A for aneuploidy detection. Am J Obstet Gynecol 181, 887–892.[CrossRef][ISI][Medline]