Origin and Differentiation of Androgen-Producing Cells in the Gonads

Abstract

Sexual reproduction is dependent on the activity of androgenic steroid hormones to promote gonadal development and gametogenesis. Leydig cells of the testis and theca cells of the ovary are critical cell types in the gonadal interstitium that carry out steroidogenesis and provide key androgens for reproductive organ function. In this chapter, we will discuss important aspects of interstitial androgenic cell development in the gonad, including: the potential cellular origins of interstitial steroidogenic cells and their progenitors; the molecular mechanisms involved in Leydig cell specification and differentiation (including Sertoli-cell-derived signaling pathways and Leydig-cell-related transcription factors and nuclear receptors); the interactions of Leydig cells with other cell types in the adult testis, such as Sertoli cells, germ cells, peritubular myoid cells, macrophages, and vascular endothelial cells; the process of steroidogenesis and its systemic regulation; and a brief discussion of the development of theca cells in the ovary relative to Leydig cells in the testis. Finally, we will describe the dynamics of steroidogenic cells in seasonal breeders and highlight unique aspects of steroidogenesis in diverse vertebrate species. Understanding the cellular origins of interstitial steroidogenic cells and the pathways directing their specification and differentiation has implications for the study of multiple aspects of development and will help us gain insights into the etiology of reproductive system birth defects and infertility.

The Insulin/IGF System in Mammalian Sexual Development and Reproduction

“…Fetal LCs (FLCs) of the testis first appear around E12.5 [27] and are thought to differentiate from several sources, including interstitial cells derived from the coelomic epithelium and migrating cells derived from the mesonephros [28]. FLCs are responsible for masculinizing the male urogenital system through androgen production.…”

“…FLCs are responsible for masculinizing the male urogenital system through androgen production. However, after birth, they are gradually replaced by adult LCs (ALCs) [27], which produce the testosterone responsible for spermatogenesis, maintenance of secondary sex characteristics and fertility. In females, theca cells become distinguishable after birth upon receiving granulosa cell-derived signals [29], and produce androgens that are further converted into estrogens by the granulosa cells.…”

Insulin and IGF1 receptors are essential for the development and steroidogenic function of adult Leydig cells

“…In parallel, the bipotential gonadal primordium differentiates into a testis or an ovary, depending upon the genetic sex. Interestingly, there are 2 distinct populations of LCs during testicular development, the fetal LCs (FLCs), which appear at around E12.5, and the adult LCs (ALCs), which progressively replace FLCs during postnatal development (4). FLC and ALC expansion relies on the differentiation of proliferating progenitor LCs (PLCs), but whether those progenitors are common or distinct is still a matter of debate [reviewed in Svingen and Koopman (5)].…”

Mast cells of bulbourethral glands in children, adolescents and youth

“…Сопоставление полученных результатов с данными литературы о возрастной динамике уровня андрогенов у мужчин дает возможность судить о степени участия этих локальных регуляторов в жизнедеятельности желез в каждом из изученных возрастных периодов. У детей грудного возраста относительное число туч-ных клеток, значения ИНГ и ИД минимальны, что свидетельствует о невостребованности внутриорганных регуляторов на фоне «инфантильного выброса тестостерона», имеющего место в первый год жизни мальчиков [1][2][3]. Последующее увеличение величин этих показателей в период раннего детства, а затем в первом и втором периодах детства можно рассматривать как возрастание участия тучных клеток в морфогенезе желез на фоне низкого уровня андрогенизации организма.…”

“…Наивысшие значения всех показателей были получены для подросткового возраста, что можно трактовать как синергичное участие тучных клеток и нарастающих концентраций мужских половых стероидов в развитии и функционировании бульбоуретральных желез при становлении репродуктивной функции организма. Снижение значений ИНГ и ИД у юношей, скорее всего, отражает отсутствие необходимости иных регуляторов жизнедеятельности желез на фоне наивысшего уровня андрогенов, который характерен для этого возрастного периода [1][2][3], и может служить косвенным подтверждением высокой зависимости бульбоуретральных желез от половых стероидов.…”