Elsevier

Neuroscience

Volume 141, Issue 4, 2006, Pages 1731-1745
Neuroscience

Cellular neuroscience
Sexual dimorphism in the organization of the rat hypothalamic infundibular area

https://doi.org/10.1016/j.neuroscience.2006.05.041Get rights and content

Abstract

The hypothalamic infundibular area is located outside the blood–brain barrier and includes, the ventromedial arcuate nucleus (vmARC) sensing circulating substances, and the median eminence (ME) where neurohormones are released into the hypothalamo-hypophysial vasculature. This integrated functional unit, pivotal in endocrine control, adjusts neuroendocrine output to feedback information. Despite a differing physiology in males and females, this functional unit has not appeared differently organized between sexes.

Using immunocytochemistry, we describe here for the first time in adult rats, a conspicuous sex-difference in its axonal wiring by intrinsic glutamatergic neurons containing the neuropeptides neurokinin B (NKB) and dynorphin. In the male, NKB neurons send axons to capillary vessels of the vmARC and of the ME (only where gonadotropin-releasing hormone (GnRH) axons terminate). Electron microscopy revealed that NKB axons target the barrier of tanycytes around fenestrated capillary vessels (in addition to GnRH axons), suggesting a control of regional bidirectional permeability. In the female, NKB neurons send axons to the neuropile of the vmARC, suggesting a direct control of its sensor neurons. The other projections of NKB neurons, studied by surgical isolation of the ARC-ME complex and confocal microscopy, are not sexually dimorphic and target both integrative and neuroendocrine centers controlling reproduction and metabolism, suggesting a broad influence over endocrine function.

These observations demonstrate that the mechanisms subserving hypothalamic permeability and sensitivity to feedback information are sexually dimorphic, making the infundibular area a privileged site of generation of the male-to-female differences in the adult pattern of pulsatile hormonal secretions.

Section snippets

Experimental procedures

Preparation of brain tissue, immunocytochemical procedures and controls, were as detailed (Ciofi, 2000). All efforts were made to minimize the number of animals used and their suffering. They were anesthetized (xylazine/ketamine: 2 mg/5 mg per 100 g b.w.), operated on and killed (after an overdose of 20% chloral hydrate) in accordance with the European Communities Council Directive of 24 November 1986 (86/609/EEC). Experiments conformed to guidelines of the Comité Régional d’Ethique Aquitaine

Sexually dimorphic distribution of NKB-LI axons in the infundibular area

Throughout the rostro-caudal extent of the ARC, both sexes displayed NKB-LI perikarya in similar number and distribution and a “shared NKB-LI innervation” (more intensely labeled in females). In addition, “sex-specific” NKB-LI innervations were conspicuous (Fig. 1, Fig. 2, Fig. 3, Fig. 4). In females, more NKB-LI axonal courses with perisomatic arrangements were apparent in the vmARC/sub-ependymal zone of the ME while only isolated NKB-LI axons reached the ME external zone. In males,

Discussion

These observations suggest that the infundibular area is qualitatively different in organization between sexes. This evidence may allow progress in understanding how the hypothalamus shapes pituitary pulsatility and integrates humoral feedback: it is discriminative and concerns a region with known structure–function relationships. However, this conclusion is based on visualization of chemical phenotypes instead of true anatomical structure. Also, such a dimorphic anatomical wiring may be

Conclusion

This evidence of a qualitative sex dimorphism in the macro-organization of the hypothalamic interface with both the pituitary and the periphery makes it a privileged site of generation of the male-to-female differences in the adult pattern of pulsatile hormonal secretions. Many other neuronal systems certainly participate in the sex-specific wiring of the hypothalamus. They may not all display such a clear-cut phenotype as NKB neurons here in the rat.

Acknowledgments

We are grateful to Dr. Robert H. Edwards (Univ. California, San Francisco) for his kind gift of antiserum to VGluT2, and to Dr. Vincent Prévot (Inserm U816, Lille, France) for reading the manuscript. Supported by Inserm, La Fondation pour la Recherche Médicale and Université Victor Ségalen Bordeaux 2.

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