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J Clin Endocrinol Metab. 2012 Dec;97(12):E2210-20.
Sex diferences in the neurokinin B system in the
human infundibular nucleus.
Taziaux M, Swaab DF, Bakker J.
Abstract
CONTEXT:
The recent report that loss-of-function mutations in either the gene encoding neurokinin B
(NKB) or its receptor (NK3R) produce gonadotropin defciencies in humans strongly points to
NKB as a key regulator of GnRH release.
OBJECTIVES:
We used NKB immunohistochemistry on postmortem human brain tissue to determine:
1) whether the human NKB system in the infundibular nucleus (INF) is sexually dimorphic; 2) at
what stage in development the infundibular NKB system would diverge between men and
women; 3) whether this putative structural diference is reversed in male-to-female (MtF)
transsexual people; and 4) whether menopause is accompanied by changes in infundibular NKB
immunoreactivity.
METHODS:
NKB immunohistochemical staining was performed on postmortem hypothalamus material of
both sexes from the infant/pubertal period into the elderly period and from MtF trans-
sexuals.
RESULTS:
Quantitative analysis demonstrated that the human NKB system exhibits a robust female-
dominant sexual dimorphism in the INF. During the frst years after birth, both sexes displayed
a moderate and equivalent level of NKB immunoreactivity in the INF. The adult features
emerged progressively around puberty until adulthood, where the female-dominant sex
diference appeared and continued into old age. In MtF transsexuals, a female-typical NKB
immunoreactivity was observed. Finally, in postmenopausal women, there was a signifcant
increase in NKB immunoreactivity compared to premenopausal women.
CONCLUSION:
Our results indicate that certain sex diferences do not emerge until adulthood when acti-
vated by sex steroid hormones and the likely involvement of the human infundibular NKB
system in the negative and positive feedback of estrogen on GnRH secretion.
Sex diferences in the Neurokinin B system in the human infundibular nucleus (INF).
(A) NKB expression during lifespan in men and women. During the frst years after birth, both sexes
displayed a moderate and equivalent level of NKB expression in the INF. The adult features emerged
progressively around puberty until adulthood, where the female-dominant sex diference appears and
continued into old age. (B) Example of NKB expression in men (right panel, 33 yr old) vs. women (left
panel, 34 yr old). (C) Human male-to-female transsexuals have a female-like NKB expression. (D) Increase
and hypertrophy of neurons expressing NKB in postmenopausal women (right panel, 90 yr old) compared
with premenopausal women (left panel, 34 yr old) in the INF.