Molecular profiling of postnatal development of the hypothalamus in female and male rats1
Open accessAbstract
Reproductive function is highly dynamic during postnatal developmental. Here, we performed molecular profiling of gene expression patterns in the hypothalamus of developing male and female rats to identify which genes are sexually dimorphic, to gain insight into a more complex network of hypothalamic genes, and to ascertain dynamic changes in their relationships with one another and with sex steroid hormones during development. Using a low-density PCR platform, we quantified mRNA levels in the preoptic area (POA) and medial basal hypothalamus (MBH), and assayed circulating estradiol, testosterone, and progesterone at six ages from birth through adulthood. Numerous genes underwent developmental change, particularly postnatal increases, decreases, or peaks/plateaus at puberty. Surprisingly, there were few sex differences; only Esr1, Kiss1, and Tac2 were dimorphic (higher in females). Cluster analysis of gene expression revealed sexually dimorphic correlations in the POA but not the MBH from P30 (Postnatal Day 30) to P60. Hormone measurements showed few sex differences in developmental profiles of estradiol; higher levels of progesterone in females only after P30; and a developmental pattern of testosterone with a nadir at P30 followed by a dramatic increase through P60 (males). Furthermore, bionetwork analysis revealed that hypothalamic gene expression profiles and their relationships to hormones undergo dynamic developmental changes that differ considerably from adults. These data underscore the importance of developmental stage in considering the effects of hormones on the regulation of neuroendocrine genes in the hypothalamus. Moreover, the finding that few neuroendocrine genes are sexually dimorphic highlights the need to consider postnatal development from a network approach that allows assessment of interactions and patterns of expression.
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Testosterone is significantly higher in males than females on PD 40; whereas estradiol has just started to be released.
“Testosterone is significantly higher in males than females on PD 40; whereas estradiol has just started to be released (34).”
From Puberty Blocker, Leuprolide, Reduces Sex Differences in Rough-and-Tumble Play and Anxiety-like Behavior in Juvenile Rats (2024) · cites this paper as [34]
The Results report significantly higher testosterone in males at the measured ages except P30, but the study did not measure PD40 specifically. The Results and Discussion contradict the estradiol claim: estradiol was already present, peaked at P15 in both sexes, and decreased as the rats matured. Page numbers are not available in our copy. (LLM, conf=0.88)
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The neural basis of puberty and adolescence
Sisk, C. L., & Foster, D. L. (2004) · Nature Neuroscience · doi:10.1038/nn1326 · Cited by 1,085 · cited 1× · see citing works
“Considering that the brain remains sensitive to steroid hormones postnatally [24], during which time there are large changes in both hormone and neurotransmitter release, this is an important gap in research.”
BackgroundNavarro, V. M., Gottsch, M. L., Wu, M., García-Galiano, D., Hobbs, S. J., Bosch, M. A., Pinilla, L., Clifton, D. K., Dearth, A., Ronnekleiv, O. K., et al. (2011) · Endocrinology · doi:10.1210/en.2011-1143 · Cited by 254 · see citing works
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- Authors
- Walker, D. M., Kirson, D., Perez, L. F., & Gore, A. C.
- Affiliations
- The University of Texas at Austin (US)
- Venue
- Biology of Reproduction
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-12-01
- Volume
- 87
- Issue
- 6
- Pages
- 129-129
- ISSN
- 0006-3363 (ISSN-L)
- 1529-7268
- PMC
- PMC4435423
- OpenAlex
- W2140123938
- Cited by
- 72
- References
- 4
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 5 · 2023: 5 · 2022: 1 · 2021: 5 · 2020: 3 · 2019: 5 · 2018: 6 · 2017: 6 · 2016: 5 · 2015: 8 · 2014: 10 · 2013: 6
- FWCI
- 8.97
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biology of Reproduction (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- BioOne Complete (BioOne) (submittedVersion)
- Funders
- Georgia Institute of Technology
- National Institutes of Health (5r01es020662-05)
- National Institute on Aging (F31AG034813)
- National Institute of Environmental Health Sciences (R01-ES020662, 1R01 ES020662, RC1ES018139)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Keywords
- hypothalamus, postnatal development, sexual dimorphism, gene expression profiling, preoptic area, medial basal hypothalamus, sex hormones, puberty, estradiol, testosterone, progesterone, KISS1, ESR1
- MeSH terms
- Animals, Animals, Newborn, Estradiol, Female, Hypothalamus, Hypothalamus, Middle, Male, Nerve Tissue Proteins, Neurons, Preoptic Area, Progesterone, Sex Characteristics, Sexual Maturation, Testosterone, Neurokinin B, Rats, Sprague-Dawley, Gene Expression Regulation, Developmental, Gene Expression Profiling, Estrogen Receptor alpha, Rats, Neurogenesis, Kisspeptins
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