DOPAMINE RECEPTORS IN MALE AND FEMALE REPRODUCTIVE SYSTEMS
Overall features of the reproductive system
The reproductive axis in both genders comprises the hypothalamus, pituitary, gonads, and the reproductive tract, all of which are functionally connected via feed-forward and feed-back interactions between central and peripheral hormones. Expression of DARs in the hypothalamus and pituitary gland is covered in Chapters 4 and 5. To recapitulate this information, reproduction in both males and females is centrally controlled by gonadotropin-releasing hormone (GnRH)-producing neurosecretory neurons with cell bodies in the preoptic area of the hypothalamus and axon terminals in the median eminence. GnRH is released from these terminals in a pulsatile manner into the hypophysial portal blood and is delivered to the anterior pituitary. Within the pituitary, GnRH binds to GnRH receptors on the gonadotrophs and regulates the release of the gonadotropins, luteinizing hormone (LH) and follicle- stimulating hormone (FSH). Both hormones differentially promote sexual differentiation, affect secondary sex characteristics, gonadal development, gametogenesis, and regulate the fertility in both sexes. In addition to the gonadotropins, prolactin (PRL) exerts diverse actions in females during the reproductive cycle, pregnancy, and lactation, and its pathological overproduction interferes with many reproductive processes in both genders. Below we focus on DAR expression in the gonads and the reproductive tracts of both males and females.
The male lower reproductive system
The male lower reproductive system includes the testes (gonads), epididymis, vas deferens, ejaculatory duct, urethra, seminal vesicles, prostate, bulbourethral glands, and penis. Different DAR subtypes are expressed in testes from several species. Within the seminiferous tubules of the rat testis, D2R is expressed in all pre- and post-meiotic germ cells, with the highest expression in spermatogonia, the undifferentiated male germ cells [76]. The same investigators also detected D2R protein in isolated spermatogenic cells and spermatozoa from rats, mice, bulls, and humans. Confocal microscopy of mature spermatozoa has showed that D2R was primarily localized in the flagellum, but also in the acrosome of the sperm head, except in human spermatozoa [76]. As illustrated in Figure 6.12, D2R was localized in the acrosome, mid piece, and flagellum in boar sperm and was activated during in vitro capacitation [77]. There are no published data on expression of DAR other than D2R in the testis.
Figure 6.12 Schematic representation of the boar sperm cell. Panel A: Sectional view of a sperm cell. Solid lines represent membrane bilayers:
1, acrosome; 2, nuclear envelope; 3, nucleus; 4, posterior ring and neck; 5, mitochondria; 6, annular ring; Panel B: Surface view of the sperm head and midpiece with the subdomains. Panel C: The acrosome reaction. 7, mixed vesicles that are formed during the acrosome reaction via multiple fusions between the plasma membrane and the outer acrosomal membrane. (Redrawn and modified from Gadella, B.M. et al., Int J Dev Biol., 52, 473-480, 2008.)
There is only scant information on DAR expression in the male extra- gonadal reproductive tract. An early study used a combination of radioreceptor binding and autoradiography to examine the localization of the DA agonist 3H-dihydroergotoxine in rat male sex organs. The drug was bound to smooth muscle cells of the vas deferens, seminal vesicles, and prostate gland, as well as to glandular tissue of the seminal vesicles and prostate gland [78]. These findings were supported by a later study showing the presence of DIR and D2R transcripts in human and rat seminal vesicles [79]. Both D2R [80] and D4R [81] were expressed in the guinea pig vas deferens, while D2R was detected in vas deferens from mice but not rats [82].
The human corpus cavernosum penis is a highly vascularized tissue which fills with blood during erection. D1R was twofold more abundant than D2R in this tissue, and both were primarily localized in the smooth muscle component of this structure [83].
