Studies on the cortical cells of human fetal adrenals in tissue culture

Kahri, Arvi; Halinen, H.

doi:10.1159/000144257

Cited by 16 publications

(4 citation statements)

References 2 publications

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“…Similar findings have been described by Khari and his co-workers (27,9,28). We find that after 5 days of culture there is greater variability in the shape of the mitochondria than that noted by Kahri and Halinen (27) but the internal structure resembles that of zona glomeruIasa mitochrondria.…”

Section: Discussionsupporting

confidence: 91%

Control of steroid synthesis in human fetal adrenals in monolayer culture

Baird¹,

Brisson²,

Kan³

et al. 1978

Can. J. Biochem.

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S. (1978) Control of steroid synthesis in human fetal adrenals in monol;myer culture. Can. 9. Bioclaern. 56,577-584The actions of adrenocorticotrophin 1-39 (ACTH), N6,02-dibutyryl adenosine-3',5'-cyclic phosphate (dbcAMP), and human chorionic gonadotrophin (hCG) on the sulfation of DHA and the synthesis of cortisol by human fetal adrenal cells in monolayer culture have been described. Electron microscopic studies indicate that the cells present in our cultures at the end of 5 days are intact and have many of the characteristics of secretory cells. Sulfation of DHA was strongly inhibited by 11-deoxycorticosterone, testosterone, androsterone, and dihydrotestosterone. Very small effects were observed with progesterone and corticosterone and insignificant effects with estrone, estradiol, and estriol. Androstenedione as well as 17a-hydroxylated corticosteroids showed no inhibition. When used as substrate, C,, A4-3-ketosteroids were good precursors of cortisol with 11-deoxycortisol being the best one followed by 17a-hydroxyprogesterone and progesterone. The conversion of progesterone (4pg12 ml) to cortisol was fivefold greater than under conditions where no substrate was present (endogenous production). ACTH in the concentration of 5 x Ulml added twice daily to the cell cultures for 8 days increased eightfold the sulfation of DHA and increased cortisol synthesis from progesterone 35-fold in 5 days. The addition of dbcAMP (5 x lW5 M ) or hCG used at 2.0 or 0.2 Ulml did not stimulate the sulfation of DHA. A lag period of at least 36 h is required before the stimulation of DHA sulfation or cortisol synthesis from progesterone can be observed. dbcAMP can stimulate the conversion of progesterone, 17a-hydroxyprogesterone, and I I-deoxycortisol to cortisol by the adrenal cells. These data suggest that 1 la-and 21-hydroxylation are stimulated by dbcAMP but 17a-hydroxylation is not altered.

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Section: Discussionsupporting

confidence: 91%

Control of steroid synthesis in human fetal adrenals in monolayer culture

Baird¹,

Brisson²,

Kan³

et al. 1978

Can. J. Biochem.

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“…Thus, there is marked atrophy of the fetal adrenal gland when pituitary ACTH release is suppressed by administration of synthetic corticosteroids in the human (Mesiano & Jaffe 1992), baboon (Leavitt et al 1997, Aberdeen et al 1998, and rhesus monkey (Challis et al 1974). Depending upon the experimental conditions employed in culture studies, however, ACTH had either inhibitory (Ramachandran & Suyama 1975, Hornsby & Gill 1977, Simonian & Gill 1981, stimulatory (Kahri & Halinen 1974, Roos 1974), or limited (Di Blasio et al 1990) effects on the proliferation of human fetal adrenocortical cells, and caused hypertrophy of the primate fetal adrenal cortex (Coulter et al 1996). Other peptides of placental or fetal origin, e.g.…”

Section: Discussionmentioning

confidence: 99%

Developmental expression of cell cycle regulators in the baboon fetal adrenal gland

Dumitrescu

Aberdeen

Pepe

et al. 2007

Journal of Endocrinology

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Although the human and the nonhuman primate fetal adrenal glands undergo a highly unique pattern of cortical zonespecific intrauterine growth and development, studies of the regulatory components of the cell cycle responsible for this growth have not been conducted. Therefore, the present study determined expression of the cell cycle regulators, cyclin D1 and cyclin E, and their cyclin-dependent kinases, Cdk2, Cdk4, and Cdk6, and Ki67 a marker of cell proliferation within the baboon fetal adrenal cortex during advancing stages of gestation. Fetal adrenal glands were obtained on days 60 (early), 100 (mid), and 160-170 (late) of gestation (termZ184 days). Mean (GS.E.) cyclin D1 mRNA levels, determined by RT-PCR and expressed relative to 18S rRNA, were similar at early (0 . 85G0 . 09) and mid (1 . 04G 0 . 08) gestation, then decreased (P!0 . 001, ANOVA) approximately 50% by late gestation (0 . 57G0 . 04). Cyclin E mRNA levels were also similar at early (2 . 03G0 . 07) and mid (1 . 63G0 . 31) gestation, and decreased by 70% (P!0 . 001) in late gestation (0 . 53G0 . 09). Coinciding with the decrease in cyclin D1 and cyclin E, the percentage of Ki67 positive cells in the definitive zone decreased twofold (P!0 . 01) between mid (28 . 2G3 . 6) and late (13 . 8G1 . 7) gestation. The cyclin D1 and cyclin E proteins, determined by immunocytochemistry, were expressed at high levels in the definitive zone of baboon fetal adrenal gland, where they decreased between mid-and late gestation. In contrast, immunocytochemical expression of the functionally important steroidogenic enzyme D 5 -3b-hydroxysteroid dehydrogenase (3b-HSD) became abundant in the definitive and transitional zones with advancing pregnancy. However, fetal adrenal Cdk2, Cdk4, and Cdk6 mRNA levels and protein immunoexpression were similar in the baboon fetal adrenal at early-, mid-, and late gestation. In summary, expression of cyclin D1, cyclin E, and Ki67 decreased, while 3b-HSD expression increased, in the fetal adrenal cortex, particularly in the definitive zone, between mid-and late-baboon gestation. We propose that a developmental decline in cellular proliferation permits functional differentiation of fetal adrenal cortical cells, leading to increased production of steroid hormones important for placental estrogen synthesis and maturation of organ systems within the developing fetus.

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“…Early HFA cell cultures focused on in vitro growth conditions and regulation of steroid hormone synthesis (Stark et al 1965;Milner and Villee 1970;Kahri and Halinen 1974). Interestingly, early HFA cells were also used to examine the toxicological effects of o,p1-DDD (later to become the adrenal cancer treatment drug mitotane) (Komissarenko et al 1971a, b).…”

Section: Fetal Adrenal Primary Culturesmentioning

confidence: 99%

“…Interestingly, early HFA cells were also used to examine the toxicological effects of o,p1-DDD (later to become the adrenal cancer treatment drug mitotane) (Komissarenko et al 1971a, b). The availability of primary cultures of HFA cells allowed researchers to establish the role of ACTH and its signaling cascade (cyclic AMP; cAMP) in the regulation of steroid enzyme activity and steroid hormone production (Kahri and Halinen 1974;Roos 1974;Goodyer et al 1976;Kahri et al 1976;Turchin and Mellina 1976;Baird et al 1978;Voutilainen 1979;Voutilainen and Kahri 1979). Following the isolation and subsequent cloning of the genes encoding steroidogenic enzymes, HFA cells were used to define the mechanisms controlling transcription of the enzymes needed for steroid hormone synthesis which included ACTH as well as insulin-like growth factor II (IGF-2) (Ohashi et al 1983;Mason et al 1986;Di Blasio et al 1987;Voutilainen and Miller 1988;Doody et al 1990;Lebrethon et al 1994;.…”

Section: Fetal Adrenal Primary Culturesmentioning

confidence: 99%

Primary Cultures and Cell Lines for <i>In Vitro</i> Modeling of the Human Adrenal Cortex

Nanba

Blinder

Rainey

2021

Tohoku J. Exp. Med.

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The human adrenal cortex is a complex endocrine organ that produces mineralocorticoids, glucocorticoids and androgens. These steroids are produced in distinct cell types located within the glomerulosa, fasciculata and reticularis of the adrenal cortex. Abnormal adrenal steroidogenesis leads to a variety of diseases that can cause hypertension, metabolic syndrome, infertility and premature adrenarche. The adrenal cortex can also develop steroid-producing adenomas and rarely adrenocortical carcinomas. In vitro cell culture models provide important tools to study molecular and cellular mechanisms controlling both the physiologic and pathologic conditions of the adrenal cortex. In addition, the presence of multiple steroid-metabolizing enzymes within adrenal cells makes it a model for defining possible endocrine disruptors that might block these enzymes. The regulation and dysregulation of human adrenal steroid production and cell division/tumor growth can be studied using freshly isolated cells but this requires access to human adrenal glands, which are not available to most investigators. Immortalized human adrenocortical cell lines have proven to be of considerable value in studying the molecular and biochemical mechanisms controlling adrenal steroidogenesis and tumorigenesis. Current human adrenal cell lines include the original NCI-H295 and its substrains: H295A, H295R, HAC13, HAC15, HAC50 and H295RA as well as the recently established MUC-1, CU-ACC1 and CU-ACC2. The current review will discuss the use of primary cultures of fetal and adult adrenal cells as well as adrenocortical cell lines as in vitro models for the study of human adrenal physiology and pathophysiology.

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Studies on the cortical cells of human fetal adrenals in tissue culture

Cited by 16 publications

References 2 publications

Control of steroid synthesis in human fetal adrenals in monolayer culture

Control of steroid synthesis in human fetal adrenals in monolayer culture

Developmental expression of cell cycle regulators in the baboon fetal adrenal gland

Primary Cultures and Cell Lines for <i>In Vitro</i> Modeling of the Human Adrenal Cortex

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