Neurotensin‐lmmunoreactive Neurons in the Rat Medial Preoptic Area are Oestrogen‐Receptive

Abstract

The identity of neurons influenced by oestrogen is critical for the understanding of ovarian steroid actions in the brain. The medial preoptic a r e a (MPOA) contains one of the largest oestrogen-receptive cell populations in the rat brain and participates in several oestrogen-dependent functions, including the regulation of luteinizing hormone (LH) secretion and sexual behaviour. Using double immunostaining procedures with antibodies specific for the oestrogen receptor and neurotensin, a neuropeptide implicated in the regulation of LH secretion within this area, we found that approximately half of the neurotensin-immunoreactive neurons in the MPOA also displayed immunoreactivity for the oestrogen receptor. We estimate that oestrogen-receptive neurotensin neurons represent 5% to 12% of all oestrogen receptor-positive cells in the MPOA. Our results provide morphological evidence that neurotensin mediates oestrogendependent mechanisms within the brain and suggest that oestrogen may act through preoptic neurotensin neurons to aid in the generation of the LH surge.The MPOA contains one of the largest populations of oestrogenreceptive neurons in the rat brain (1, 2) and plays a key role in reproductive neuroendocrine (3) and behavioural (4) pathways, both of which are oestrogen-dependent. In order to understand how oestrogen modulates neural activity within the MPOA it is necessary to identify the neural populations influenced by this ovarian steroid. This need is highlighted by our present understanding of how oestrogen controls the secretion of LH. Although oestrogen is known to act in the MPOA to evoke the preovulatory LH surge (3, 5), the LH-releasing hormone (LHRH) neurons themselves are unable to concentrate oestrogen (6). Until now, the only identified oestrogen-receptive population in the MPOA has been one containing the inhibitory neurotransmitter ?-aminobutyric acid (GABA) (7). Recent work suggests that GABA neurons in the MPOA are partly responsible for mediating feedback effects of oestrogen to the LHRH neurons and generating the LH surge (8)(9)(10). However, the neurochemical nature of the other oestrogen-receptive cells in the MPOA must be determined before a full understanding of oestrogen actions in this area is attained.Within the MPOA, neurotensin appears to be important in modulating the activity of LHRH neurons at the time of the LH surge. Neurotensin exerts a stimulatory influence on the magnitude of the LH surge (1 1, 12) and oestrogen modulates neurotensin/neuromedin N mRNA expression within the MPOA of ovariectomized rats (1 3). These observations suggest that neurotensin-containing neurons in the MPOA are a target for oestrogen in stimulating the activity of LHRH neurons. As the distribution of neurotensin-immunoreactive neurons in the MPOA (14, 15) appears to overlap that of the oestrogen-receptive cells (1, 2), we investigated the possibility that neurotensin neurons are another oestrogen-receptive population in the MPOA.In agreement with earlier studies (2, 16, 17) using the now well chara...

Immunocytochemical Identification of Oestrogen Receptors in Preoptic Neurones Containing Calcitonin Gene-Related Peptide in the Male and Female Rat

“…As previously shown by ourselves and others [4,8], a large population of cells in the MPOA have oestrogen re ceptor-1R nuclei. Ihese cells are concentrated rostrally in the AVIA and more caudallv in the region of the periven tricular preoptic nucleus and MPN.…”

“…We do not, at present, know if CGRP is syn thesised by the same preoptic neurones containing GABA or neurotensin. However, unlike neurotensin [8] and GABA [7], the majority of CGRP-IR cells in the fe male MPN are oestrogen-receptive. It is interesting to note that gonadal steroid hormones modulate cells syn thesising CGRP elsewhere in the central nervous system [15] and periphery [12].…”

“…Recent studies in the preoptic area have shown that terminals containing luteinising hormone-releasing hormone (LHRH) synapse on neurones with oestrogen receptors [5] and that some oestrogen-receptive neurones project to the ventromedial nucleus [6]. Studies have also demonstrated that GABA [7] and neurotensin [8] are synthesised within subpopula tions of preoptic neurones with oestrogen receptors.Recent work has identified a large population of neu rones containing calcitonin gene-related peptide (CGRP) in the MPOA of the female rat [9]. This population is of Dr. A.E.…”

Progesterone Receptor and Neurotensin Are Colocalized in Neurons of the Guinea Pig Ventrolateral Hypothalamus

“…In the preoptic area it has been recently demonstrated that 25-50% of the NT-immunoreactive (NT-IR) neurons contain estrogen receptors [19,20]. This coexistence suggests that in the preoptic area NT neurons mediate directly stimulatory effects of ovarian steroids on Gn-RH secretion.…”

Distribution of Estrogen Receptor-Immunoreactive Cells in the Preoptic Area of the Ewe: Co-Localization with Glutamic Acid Decarboxylase but Not Luteinizing Hormone-Releasing Hormone

“…In the rat, the preoptic area (POA) contains the largest numbers of ER-IR cells [7] and several studies have been undertaken to establish the neurotransmitters used by estrogen-re ceptive neurons in this area [13][14][15][16] and define their neuroanatomical connections [17][18][19]. Although the LHRH neurons responsible for the LH surge in the rat are known to reside in the POA, they do not possess ERs [15,20] and it is believed that estrogen modulates their activity indirectly.…”