The Secretion of Human Chorionic Gonadotropin as well as theα- andβMessenger Ribonucleic Acid Levels Are Stimulated by Exogenous Gonadoliberin Pulses Applied to First Trimester Placenta in a Superfusion Culture System

Abstract

It is well documented that the hypothalamic decapeptide gonadoliberin (GnRH) controls the biosynthesis and secretion of pituitary gonadotropins; however, it is still unclear whether GnRH synthesized by the placenta plays the same role with respect to hCG. In the current study we have investigated the acute response of placenta tissue to a single GnRH pulse as well as the influence of GnRH pulses on the secretion of hCG and hCG mRNA concentrations elicited several hours after application of the peptide hormone. For this purpose we have used a superfusion culture model of first trimester placenta tissue (8-12 weeks of gestation). In the first hour after explantation of the tissue, hCG secretion was decreased, and increasing amounts of free subunits were released. Afterward, the original hCG secretion rates were recovered and maintained for several days, attended by decreased levels of free subunits in the culture medium. The superfusion model was superior to static incubations, since it showed approximately a 4-fold higher amount of hCG to be secreted within 24 h (day 3 of cultures). A single GnRH pulse (1 mumol/L; 30 min) caused a significantly increased transient release of hCG (P less than 0.0001). Two GnRH pulses (concentration range, 0.01-10 mumol/L; 30 min) applied 24 h after (first pulse) and in the interval between 36-48 h after (second pulse) the start of the superfusion culture elicited a long-lasting 2-fold increase in the hCG secretion rate, which rose approximately 6 h after the second GnRH pulse. This was correlated with increased mRNA concentrations measured by means of Northern blots of total RNA. At 0.02 mumol/L GnRH, 4-fold higher beta mRNA levels were observed. The alpha mRNA levels were 2.5-fold elevated. GnRH pulses of 0.01 and 10 mumol/L, respectively, were ineffective. A further effect of GnRH pulses was augmentation of the episodic character of hCG secretion. Our results suggest that GnRH causes different specific acute and late effects on the amount and pattern of hCG secretion as well as on hCG biosynthesis at the levels of both hCG subunit mRNAs.

On the Role of Human Chorionic Gonadotropin (hCG) in the Embryo-Endometrial Microenvironment: Implications for Differentiation and Implantation

“…This increase probably reflects the progressive differentiation of cytotrophoblasts that produce little hCG to syncytiotrophoblasts that produce high amounts of hCG. In addition, other regulatory mechanisms within the placenta such as gonadotropin-releasing hormone (GnRH), 20 ␥-aminobutyric acid (GABA), 21 EGF, 22 and others 23 may be involved in the regulation of this increase. At an unknown point of time during the course of differentiation, the hCG/LH receptor expression may be switched to the full-length form.…”

“…To fully activate angiogenesis, a pulsatile hCG application may be necessary as is physiologically seen during pregnancy. 20,21,43…”

Administration d’agonistes de la GnRH (Gonadotrophin Releasing Hormone) en phase lutéale des protocoles substitutifs de transferts d’embryons congelés : étude prospective randomisée

“…Les sé cré tions d'HCG par le trophoblaste sont augmenté es en cas d'ajout d'agonistes. Au contraire, elles diminuent en cas d'ajout d'antagonistes in vitro [43] comme in vivo [44,45].…”

Disulfide Bond Formation Is Not Required for Human Chorionic Gonadotropin Subunit Association

“…The fraction of the ␣-subunit being associated with the ␤-subunit in a dimer, however, is coprecipitated with this antibody. After depleting the PNS of the ␤-subunit, their precursors, and the ␣␤-dimer, the supernatant of the same PNS was used for subsequent immunoprecipitation with a goat anti-␣-hCG antibody (34,35). The immunoprecipitation with each of the antibodies was carried out for 2 h at 4°C.…”