**7. References**

84 Sex Steroids

hypothalamus (Berelowitz et al, 1982) were demonstrated to show circadian rhythmicity and suggest that the SCN may play a role in this diurnal change in SOM peptide transport from the PeVN to the ME. Thus, our data suggest that in the young female Wistar rat SOM cells in the PeVN are influenced by at least the SCN and E2. E2 may affect intrahypothalamic SOM projections within the PeVN or to other hypothalamic areas that contain SOM receptors (Beaudet et al, 1995; Hervieu et al, 1999), whereas SOM release from the ME may be influenced by the SCN. SOM content and release from hypothalamic explants is influenced by sex and age (Ge et al, 1989). The rostro-caudal distribution pattern of SOM-ir cells and the total number of SOM-ir cells in the PeVN was different in the middle-aged compared to young rats, but only 2 h after E2 treatment. These findings suggest that with age, E2 may become more crucial for the synthesis and/or storage of SOM peptide in the

The function of a diurnal change in SOM levels in the PeVN remains speculative. A few studies reported more pronounced GH secretory bursts in cycling female rats after the onset of darkness (Clark et al, 1987; Pincus et al, 1996), suggesting that the shift in the rostro-caudal SOM cell distribution at ZT11, i.e. just before dark onset, may reflect this shift in GH secretion pattern. Although to our knowledge no data exist on light/dark-related GH secretory patterns during aging, mean plasma GH levels and mean peak GH levels were found to be decreased already in 11 month old compared to young females (Takahashi et al, 1987). Taking these findings into consideration, we suggest that the changes in SOM-ir levels within the PeVN

In the present study we clearly demonstrate a significant attenuation of the LH surge at the age of 8.5 compared to 4 months old regular 4-day cycling females. This attenuation of the LH surge was not accompanied by changes in the releasable pool of LH, timing of the surge, GnRH priming or preovulatory P levels, supporting the notion that an attenuation of the LH surge may result from a change in the hypothalamic drive. Strikingly, we found clear changes in hypothalamic SOM peptide regulation following a physiological dose of estrogen in middle-aged animals. We hypothesize that the age dependent effects of an E2 stimulus on SOM-ir cell distribution and SOM-ir numbers indicate alterations in the regulation of hypothalamic SOM peptide release in response to estrogen feedback could underlie an attenuation of the LH surge with age. These observations suggest that changes in the regulation of the GH axis with age indeed coincide with the process of reproductive aging in the female rat and suggest that the proposed interaction between these neuroendocrine axes

The authors would like to thank Hans J.M. Swarts (Dept Animal Sciences, Wageningen University) for expert technical assistance and Prof Victor M. Wiegant (Dept Pharmacology, Med Fac, Utrecht University Medical Centre) for critically reviewing earlier versions of the manuscript. Current affiliations of the authors are: Danone Research, Centre for Specialised Nutrition, Singapore (EMvdB) and Wageningen, the Netherlands (BJMvdH); Notox B.V., Den Bosch, The Netherlands (HHvV) and Dept. Anatomy, Radboud University Nijmegen

PeVN and affect the diurnal change in SOM levels within the PeVN.

may translate into changes in GH release patterns during aging in female rats.

may occur via alterations in hypothalamic somatostatin release.

**5. Conclusion** 

**6. Acknowledgements** 

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**5** 

**Telocytes in Human Fallopian Tube and Uterus** 

**Express Estrogen and Progesterone Receptors** 

Evidence has accumulated over a number of years for the existence of a new cell type found in cavitary and parenchimatous organs - called telocytes (TCs). The cell biology of TCs, and especially their function is a rapidly growing area of biomedical research (Figure 1) (freeaccess data is available at www.telocytes.com). TCs are also present in fallopian tube

Progress in cellular and molecular techniques led to the identification of subtypes and isoforms of estrogen receptors (ER) (Green et al., 1986; Kuiper et al., 1996; Tremblay et al., 1997) and progesterone receptors (PR) (Kastner et al., 1990; Giangrande & McDonnell, 1999) in the female reproductive tract, two for each receptor (ERα and β, and PR A and B). Cells of the female reproductive tract are subject to hormonal control via sex steroids receptors. Subsequently, we investigated the expression of estrogen receptor (ER) and progesterone receptor (PR) in cell cultures enriched in TCs, obtained from the muscle coat of both the

In 2005, we described a new cell type which we called interstitial Cajal-like cells (ICLC) due to their similarity with canonical gastrointestinal interstitial cells of Cajal (ICC). By using electron microscopy, immunohistochemstry and cell cultures, we revealed that ICLC have particular features that distinguish and separate them from the ICC and/or other interstitial cells. Given these new findings, Popescu renamed ICLC to TELOCYTES (TCs) (Popescu & Faussone-Pellegrini, 2010) by using the Greek affix 'telos', meaning "goal", "end", and "fulfilment", suggesting cells with a particular goal, accomplished through their extremely long prolongations. The new term aims to avoid any confusion between these cells and other interstititial cells such as fibroblasts, mesenchymal cells, and myofibroblasts. The very long and thin prolongations emitted by TCs were re-defined as telopodes (TPs). TPs are built of alternating thin segments known as podomers (≤ 200 nm, below the resolving power of light microscope) and dilated segments called podoms (with a mean width of 462.31 nm),

which accommodate mitochondria, rough endoplasmic reticulum and caveolae.

(Popescu et al., 2005a) and uterine walls (Ciontea et al., 2005).

**1. Introduction** 

fallopian tube and uterus.

**2. The concept of telocytes** 

Sanda M. Cretoiu1,2, Dragos Cretoiu1,2,

*2Victor Babes National Institute of Pathology* 

*3Filantropia Hospital* 

*Romania* 

Anca Simionescu3 and Laurentiu M. Popescu1,2 *1Carol Davila University of Medicine and Pharmacy* 

