In VivoRegulation of FSH Synthesis by Inhibin and Activin

Abstract

The effect of a single sc injection of the gonadal peptide, recombinant human activin A (rhActivin A), on gonadotropin synthesis and secretion was examined in adult and immature male and female rats and the effect of recombinant human inhibin A (rhInhibin A) was examined in adult male rats. Pituitary FSH beta, LH beta and alpha messenger RNA (mRNA) levels were determined by blot hybridization. Trunk blood was collected to measure serum FSH levels. Treatment with rhInhibin A (100 micrograms/kg) resulted in a decrease in FSH beta mRNA to 2% of controls levels 6 h after injection. FSH beta mRNA levels started to rebound at 10 h, but were still significantly lower than vehicle-treated controls. Serum FSH levels were significantly reduced at 2 h and were reduced further at 6 and 10 h. There were no significant changes in alpha and LH beta mRNA levels. RhActivin A, at the highest dose (500 micrograms/kg), in immature male rats had only a modest effect (1.2- and 1.3-fold increase) on FSH beta mRNA levels and FSH secretion, respectively, at 2 h. No increase in FSH synthesis and FSH secretion was observed in adult male rats. In contrast, both immature and adult-ovariectomized E2 implanted females showed a robust response to rhActivin A. In immature females, 2 h after rhActivin A (100 and 500 micrograms/kg) administration, FSH beta mRNA levels were elevated 2.0- and 2.2-fold. At this time serum FSH was also elevated. At 6 and 10 h rhActivin A significantly reduced FSH beta mRNA levels from vehicle-treated controls. In contrast, FSH secretion was elevated at 6 h and returned to baseline at 10 h. Administration of rhActivin A (500 micrograms/kg) to adult, ovariectomized-E2 females resulted in a significant increase in FSH beta mRNA levels and FSH secretion at 2 and 6 h. There were no significant changes in alpha and LH beta mRNA levels in either males or females. Thus, these in vivo studies have shown that rhInhibin A can inhibit FSH beta mRNA levels and FSH secretion in the adult male rat. RhActivin A stimulates FSH synthesis and secretion in the immature and adult ovariectomized-E2 females, but has little or no effect in immature and adult males. Hence, there is a sexual dimorphic response to rhActivin A in vivo in the rat.

Inhibin .ALPHA., .BETA.A and .BETA.B Subunit Messenger Ribonucleic Acid Levels in Cultured Rat Pituitary: Studies by a Quantitative RT-PCR.

“…In accord with many previous reports [10][11][12][13][14] including ours [15], basal FSH secretion was increased by activin A and suppressed by inhibin A. No significant change was observed in 3 mRNA levels accompanying changes in FSH and LH secretion, though f subunit mRNA decreased to approximately half of the initial level when activin A was added, and a slight increase in a mRNA levels caused by both inhibin A and activin A. Bilezikjian et al [7] observed a significant decrease in activin f monomer and dimer production when activin A was added to rat anterior pituitary cells and proposed a local negative feedback by activin of its own production.…”

Inhibin α-Subunit N Terminus Interacts with Activin Type IB Receptor to Disrupt Activin Signaling

“…In the pituitary, FSH is stimulated by locally produced activin, and ovarianderived inhibin antagonizes activin (17,42,(45)(46)(47). Inhibin shares its ␤-subunit with activin, and can compete with activin for binding with ActRII/IIB; however, inhibin binding affinity to ActRII/IIB is 2-10ϫ lower than activin binding affinity to ActRII/IIB (6, 8, 48 -50).…”

Safety of Garcinia cambogia Extract in Healthy Volunteers: High-Dose Administration Study II

“…A slight increase of inhibin B and FSH were observed in the men. It is known that inhibin B, a dimeric gonadal glycoprotein, inhibits the pituitary secretion of FSH in a classic feedback loop, while secretion from a Sertoli cell is promoted by FSH (11)(12)(13) …”

“…However, the influences on inhibin B, FSH and other principal sex hormones and on women subjects were not investigated. Inbihib B is produced by Sertoli cells, provides negative feedback on FSH secretion and is considered to be an importan marker of spermatogenesis (11)(12)(13)(14).…”