AKAP13 Enhances CREB1 Activation by FSH in Granulosa Cells

Vaught, Kamaria C. Cayton; Hazimeh, Dana; Carter, Ashlie Sewdass; Devine, Kate; Maher, Jacqueline Y.; Maguire, M.; McGee, Elizabeth A.; Driggers, Paul H.; Segars, James H.

doi:10.1007/s43032-022-01097-5

Cited by 1 publication

(1 citation statement)

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“…In parallel to enhanced folliculogenesis, we found that the expressions of key genes associated with both follicle development ( Creb , Ccnd2 and Inhα ) and estrogen biosynthesis ( Cyp11a1 , HSD3b1 and Cyp19a1 ) in ovaries were all significantly upregulated in rats following INHα13AA-T immunization. Of these, except for HSD3b1 in granulosa cells being directly regulated by FSH [ 28 ], the other genes were all directly FSH downstream genes [ 29 , 30 ]. In contrast, the LH target ovarian steroidogenic genes ( Star [ 31 ] and Cyp17a1 [ 32 ]), as well as pituitary Lhb expression and serum LH concentrations, were all unchanged, as was reported elsewhere [ 11 , 12 , 15 , 19 , 20 , 21 , 22 ].…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Immunization against a Novel Synthetic 13-Amino Acid Betaglycan-Binding Peptide Sequence of Inhibin α Subunit on Promoting Fertility in Female Rats

Han

Xia

Chen

et al. 2023

IJMS

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Inhibins suppress the FSH production in pituitary gonadotrope cells by robustly antagonizing activin signaling by competitively binding to activin type II receptors (ACTR II). The binding of inhibin A to ACTR II requires the presence of its co-receptor, namely, betaglycan. In humans, the critical binding site for betaglycan to inhibin A was identified on the inhibin α subunit. Through conservation analysis, we found that a core 13-amino-acid peptide sequence <VRTTSDGGYSFKY> within the betaglycan-binding epitope on human inhibin α subunit is highly conserved across species. Based on the tandem sequence of such a conserved 13-amino-acid betaglycan-binding epitope (INHα13AA-T), we developed a novel inhibin vaccine and tested its efficacy in promoting female fertility using the female rat as a model. Compared with placebo-immunized controls, INHα13AA-T immunization induced a marked (p < 0.05) antibody generation, enhanced (p < 0.05) ovarian follicle development, and increased ovulation rate and litter sizes. Mechanistically, INHα13AA-T immunization promoted (p < 0.05) pituitary Fshb transcription and increased (p < 0.05) serum FSH and 17β-estradiol concentrations. In summary, active immunization against INHα13AA-T potently increased FSH levels, ovarian follicle development, ovulation rate and litter sizes, thus causing super-fertility in females. Therefore, immunization against INHα13AA is a promising alternative to the conventional approach of multiple ovulation and super-fertility in mammals.

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