The adipose-derived hormone leptin critically modulates reproductive function, such that its absence results in hypothalamic hypogonadism. Pituitary adenylate cyclase-activating polypeptide (PACAP)-expressing neurons are potential mediators of leptin's action on the neuroendocrine reproductive axis, as they are leptin-sensitive and involved in both feeding behavior and reproductive function. In the complete absence of PACAP, male and female mice exhibit metabolic and reproductive abnormalities, yet there is some sexual dimorphism in the reproductive impairments. We tested whether PACAP neurons play a critical and/or sufficient role in mediating leptin's effects on reproductive function by generating PACAP-specific leptin receptor (LepR) knockout and rescue mice, respectively. We also generated PACAP-specific estrogen receptor alpha (ERα) knockout mice to determine whether estradiol-dependent regulation of PACAP was critically involved in the control of reproductive function, and whether it contributed to the sexually dimorphic effects of PACAP. We showed that LepR signaling in PACAP neurons is critically involved in the timing of female, but not male, puberty onset, but not fertility. Rescuing LepR-PACAP signaling in otherwise LepR-deficient mice was unable to rescue the reproductive deficits observed in LepR null mice, but led to a marginal improvement in body weight and adiposity in females. Finally, PACAP-specific ERα KO did not lead to any changes in body weight or puberty onset compared to control mice. These data highlight that PACAP is a critical mediator of some of leptin's, but not estradiol's, influence on puberty onset in females, but is not critically involved in relaying leptin's effects in males or in adult females.
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 16 July 2023.
All research outputs
#21,954,040
of 27,791,073 outputs
Outputs from Endocrinology
#10,809
of 12,168 outputs
Outputs of similar age
#265,284
of 379,288 outputs
Outputs of similar age from Endocrinology
#21
of 36 outputs
Altmetric has tracked 27,791,073 research outputs across all sources so far. This one is in the 18th percentile – i.e., 18% of other outputs scored the same or lower than it.
So far Altmetric has tracked 12,168 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.5. This one is in the 9th percentile – i.e., 9% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 379,288 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 26th percentile – i.e., 26% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 36 others from the same source and published within six weeks on either side of this one. This one is in the 38th percentile – i.e., 38% of its contemporaries scored the same or lower than it.
