Immunocytochemical Investigation of Nuclear Progestin Receptor Expression within Dopaminergic Neurones of the Female Rat Brain

Abstract

Progesterone influences most processes involved in female reproduction, including ovulation, sexual behaviour, pregnancy, parturition, lactation and maternal behaviour. One neurotransmitter through which progesterone might regulate many of these functions is dopamine. To determine where in the brain progesterone might alter dopaminergic activity necessary for these and other processes in rats via cell nuclear progestin receptors, ovariectomized rats were injected subcutaneously with either 4 micro g oestradiol benzoate to induce high levels of hypothalamic progestin receptor expression, or oil, and perfused 48 h later. Dual-label immunocytochemistry was used to visualize cells having immunoreactivity (ir) for progestin receptors and tyrosine hydroxylase, a rate-limiting enzyme for dopamine synthesis. Many cells containing both progestin receptor-ir and tyrosine hydroxylase-ir were found throughout the periventricular hypothalamus of oestradiol-treated females. Conversely, very few cells in the hypothalamus of oil-treated controls contained progestin receptor-ir and, consequently, few dual-labelled cells were found in this group. The greatest percentage of tyrosine hydroxylase immunoreactive cells expressing progestin receptors in oestradiol-treated females was in, or near, the arcuate nucleus (A12 group), where up to 55% of tyrosine hydroxylase-expressing cells coexpressed progestin receptors. Notably, dual-labelled cells in oestradiol-treated females were also found more rostrally than previously reported, with approximately 15-20% of tyrosine hydroxylase-ir cells in the preoptic area/anterior hypothalamus (A14 group) also containing progestin receptor-ir. No dual-labelled cells were found for either group in the posterodorsal hypothalamus (A11 group), zona incerta (A13 group), retrorubral field (A8 group), ventral tegmental area (A10 group) or substantia nigra (A9 group) because little or no progestin receptor-ir was found in these sites. These data provide new information about the neural substrate where progesterone might regulate dopamine release in the preoptic area/anterior hypothalamus. Using more sensitive techniques than those used previously, they also confirm the relationship between progestin receptor and tyrosine hydroxylase in the arcuate nucleus, which could be important for the regulation of prolactin release throughout the female reproductive cycle. Additionally, although progesterone alters mesolimbic and nigrostriatal dopamine release, and the numerous behaviours that these pathways influence, these data again suggest that it does not do so via nuclear progestin receptor in dopaminergic cells of the ventral tegmental area and substantia nigra.

In the Ventral Tegmental Area, Progestins’ Membrane-Mediated Actions for Lordosis of Hamsters and Rats Involve Protein Kinase A

“…While these findings suggest that, in the hypothalamus, PKA-mediated increases in lordosis of E 2 -primed rodents involve PRs, there is also evidence that supports the notion that PKA has PR-independent actions for enhancing progestin-facilitated lordosis in the VTA. Notably, in the VTA, there are few intracellular PRs [55, 36] and knocking down PRs, in the VTA, with anti-sense oligonucleotides for PRs does not alter progestin-facilitated lordosis of E 2 -primed hamsters or rats [14]. However, in the current set of experiments, blocking PKA in the VTA attenuated P-mediated increases in lordosis of E 2 -primed hamsters.…”

The Vertebrate mesolimbic reward system and social behavior network: A comparative synthesis

“…The VMH is topographically located in the caudal hypothalamus along the third ventricle, is rich with sex steroid receptors (Zhang et al, 2002;Lonstein and Blaustein, 2004;Holmes et al, 2008), and is highly interconnected with the amygdala and other regions of the hypothalamus (Saper et al, 1976). The best understood function of the VMH in social behavior is its central role in regulating female receptivity.…”

In the Ventral Tegmental Area, G-Proteins and cAMP Mediate the Neurosteroid 3α,5α-THP’s Actions at Dopamine Type 1 Receptors for Lordosis of Rats

“…Progesterone (P)’s actions in the ventromedial hypothalamus (VMH) for initiating lordosis involve estradiol (E 2 )-induced intracellular progestin receptors (PRs) [1], steroid receptor coactivators [2, 3], and other actions. However, in the ventral tegmental area (VTA), P has actions to modulate lordosis intensity and duration that are independent of the few E 2 -induced PRs located there [4, 5, 6, 7]. In the VTA, limiting P’s actions to cell membranes, or blocking intracellular PRs with RU38486 or anti-sense oligonucleotides, does not reduce P’s actions, in the VTA, to facilitate lordosis of rodents [5, 8, 9].…”